MP

They all rock: A systematic comparison of conformational movements in LeuT-fold transporters. 

Licht JA, Berry SP, Gutierrez MA, Gaudet R.

Structure. 2024 Sep 5;32(9):1528-1543.e3. 

doi: 10.1016/j.str.2024.06.015. Epub 2024 Jul 17. 

PMID: 39025067.

Many membrane transporters share the LeuT fold-two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters, the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets. 

Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance. 

Kavanaugh LG, Dey D, Shafer WM, Conn GL.

Microbiol Mol Biol Rev. 2024 Sep 26;88(3):e0008923. 

doi: 10.1128/mmbr.00089-23. Epub 2024 Sep 5. 

PMID: 39235227.

The discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts. 

Unraveling the secrets: Evolution of resistance mediated by membrane proteins. 

Yang X, Li M, Jia ZC, Liu Y, Wu SF, Chen MX, Hao GF, Yang Q.

Drug Resist Updat. 2024 Aug 16;77:101140. 

doi: 10.1016/j.drup.2024.101140. Epub ahead of print. 

PMID: 39244906.

Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development. 

Determination of Initial Rates of Lipopolysaccharide Transport. 

Nava M, Rowe SJ, Taylor RJ, Kahne D, Nocera DG.

Biochemistry. 2024 Sep 12. 

doi: 10.1021/acs.biochem.4c00379. Epub ahead of print. 

PMID: 39264328.

Nonvesicular lipid trafficking pathways are an important process in every domain of life. The mechanisms of these processes are poorly understood in part due to the difficulty in kinetic characterization. One important class of glycolipids, lipopolysaccharides (LPS), are the primary lipidic component of the outer membrane of Gram-negative bacteria. LPS are synthesized in the inner membrane and then trafficked to the cell surface by the lipopolysaccharide transport proteins, LptB₂FGCADE. By characterizing the interaction of a fluorescent probe and LPS, we establish a quantitative assay to monitor the flux of LPS between proteoliposomes on the time scale of seconds. We then incorporate photocaged ATP into this system, which allows for light-based control of the initiation of LPS transport. This control allows us to measure the initial rate of LPS transport (3.0 min^-1 per LptDE). We also find that the rate of LPS transport by the Lpt complex is independent of the structure of LPS. In contrast, we find the rate of LPS transport is dependent on the proper function of the LptDE complex. Mutants of the outer membrane Lpt components, LptDE, that cause defective LPS assembly in live cells display attenuated transport rates and slower ATP hydrolysis compared to wild type proteins. Analysis of these mutants reveals that the rates of ATP hydrolysis and LPS transport are correlated such that 1.2 ± 0.2 ATP are hydrolyzed for each LPS transported. This correlation suggests a model where the outer membrane components ensure the coupling of ATP hydrolysis and LPS transport by stabilizing a transport-active state of the Lpt bridge. 

Inhibitor binding and disruption of coupled motions in MmpL3 protein: Unraveling the mechanism of trehalose monomycolate transport. 

Zhao L, Liu B, Tong HHY, Yao X, Liu H, Zhang Q.

Protein Sci. 2024 Oct;33(10):e5166. doi: 10.1002/pro.5166. 

PMID: 39291929.

Mycobacterial membrane protein Large 3 (MmpL3) of Mycobacterium tuberculosis (Mtb) is crucial for the translocation of trehalose monomycolate (TMM) across the inner bacterial cell membrane, making it a promising target for anti-tuberculosis (TB) drug development. While several structural, microbiological, and in vitro studies have provided significant insights, the precise mechanisms underlying TMM transport by MmpL3 and its inhibition remain incompletely understood at the atomic level. In this study, molecular dynamic (MD) simulations for the apo form and seven inhibitor-bound forms of Mtb MmpL3 were carried out to obtain a thorough comprehension of the protein’s dynamics and function. MD simulations revealed that the seven inhibitors in this work stably bind to the central channel of the transmembrane domain and primarily forming hydrogen bonds with ASP251, ASP640, or both residues. Through dynamical cross-correlation matrix and principal component analysis analyses, several types of coupled motions between different domains were observed in the apo state, and distinct conformational states were identified using Markov state model analysis. These coupled motions and varied conformational states likely contribute to the transport of TMM. However, simulations of inhibitor-bound MmpL3 showed an enlargement of the proton channel, potentially disrupting coupled motions. This indicates that inhibitors may impair MmpL3’s transport function by directly blocking the proton channel, thereby hindering coordinated domain movements and indirectly affecting TMM translocation. 

An in vitro set-up to study Pdr5-mediated substrate translocation. 

Gala Marti SL, Wagner M, Nentwig LM, Smits SHJ, Schmitt L.

Protein Sci. 2024 Oct;33(10):e5181. doi: 10.1002/pro.5181. 

PMID: 39312388.

Pdr5 is the most abundant ABC transporter in Saccharomyces cerevisiae and plays a major role in the pleiotropic drug resistance (PDR) network, which actively prevents cell entry of a large number of structurally unrelated compounds. Due to a high level of asymmetry in one of its nucleotide binding sites (NBS), Pdr5 serves as a perfect model system for asymmetric ABC transporter such as its medical relevant homologue Cdr1 from Candida albicans. In the past 30 years, this ABC transporter was intensively studied in vivo and in plasma membrane vesicles. Nevertheless, these studies were limited since it was not possible to isolate and reconstitute Pdr5 in a synthetic membrane system while maintaining its activity. Here, the functional reconstitution of Pdr5 in a native-like environment in an almost unidirectional inside-out orientation is described. We demonstrate that reconstituted Pdr5 is capable of translocating short-chain fluorescent NBD lipids from the outer to the inner leaflet of the proteoliposomes. Moreover, this transporter revealed its ability to utilize other nucleotides to accomplish transport of substrates in a reconstituted system. Besides, we were also able to estimate the NTPase activity of reconstituted Pdr5 and determine the kinetic parameters for ATP, GTP, CTP, and UTP. 

Transferrin receptor targeting chimeras for membrane protein degradation. 

Zhang D, Duque-Jimenez J, Facchinetti F, Brixi G, Rhee K, Feng WW, Jänne PA, Zhou X.

Nature. 2024 Sep 25. 

doi: 10.1038/s41586-024-07947-3. Epub ahead of print. 

PMID: 39322661.

Cancer cells require high levels of iron for rapid proliferation, leading to significant upregulation of cell-surface transferrin receptor 1 (TfR1), which mediates iron uptake by binding to the iron-carrying protein transferrin. Leveraging this phenomenon and the fast endocytosis rate of TfR1, we developed transferrin receptor targeting chimeras (TransTACs), a heterobispecific antibody modality for membrane protein degradation. TransTACs are engineered to drive rapid co-internalization of a target protein of interest and TfR1 from the cell surface, and to enable target protein entry into the lysosomal degradation pathway. We show that TransTACs can efficiently degrade a diverse range of single-pass, multi-pass, native or synthetic membrane proteins, including epidermal growth factor receptor, programmed cell death 1 ligand 1, cluster of differentiation 20 and chimeric antigen receptor. In example applications, TransTACs enabled the reversible control of human primary chimeric antigen receptor T cells and the targeting of drug-resistant epidermal growth factor receptor-driven lung cancer with the exon 19 deletion/T790M/C797S mutations in a mouse xenograft model. TransTACs represent a promising new family of bifunctional antibodies for precise manipulation of membrane proteins and targeted cancer therapy. 

Membranes

Synergistic effects of oxidative and acid stress on bacterial membranes of Escherichia coli and Staphylococcus simulans. 

Xie M, Koch EHW, Walree CAV, Sobota A, Sonnen AFP, Killian JA, Breukink E, Lorent JH.

Commun Biol. 2024 Sep 17;7(1):1161. 

doi: 10.1038/s42003-024-06862-7. 

PMID: 39289481.

Oxidative stress in combination with acid stress has been shown to inactivate a wide spectrum of microorganisms, including multi-resistant bacteria. This occurs e.g. in phagolysosomes or during treatment by cold atmospheric pressure plasmas (CAP) and possibly depends on the cell membrane. We therefore explored the effects of CAP-generated reactive oxygen and nitrogen species (RONS) on bacterial growth inhibition and membranes in neutral and acidic suspensions. We observed that growth inhibition was most efficient when bacteria were treated by a mix of short and long-lived RONS in an acidic environment. Membrane packing was affected mainly upon contact with short-lived RONS, while also acidity strongly modulated packing. Under these conditions, Gram-negative bacteria displayed large potassium release while SYTOX Green influx remained marginal. Growth inhibition of Gram-negative bacteria correlated well with outer membrane (OM) permeabilization that occurred upon contact with short and/or long-lived RONS in synergy with acidity. In Gram-positive bacteria, CAP impaired membrane potential possibly through pore formation upon contact with short-lived RONS while formation of membrane protein hydroperoxides was probably involved in these effects. In summary, our study provides a wide perspective on understanding inactivation mechanisms of bacteria by RONS in combination with acidity. 

Raft-like lipid mixtures in the highly coarse-grained Cooke membrane model. 

Varma M, Khuri-Makdisi F, Deserno M.

J Chem Phys. 2024 Sep 21;161(11):114103. 

doi: 10.1063/5.0230727. 

PMID: 39282832.

Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane. 

Caveolin assemblies displace one bilayer leaflet to organize and bend membranes. 

Doktorova M, Daum S, Ebenhan J, Neudorf S, Han B, Sharma S, Kasson P, Levental KR, Bacia K, Kenworthy AK, Levental I.

bioRxiv [Preprint]. 2024 Sep 4:2024.08.28.610209. 

doi: 10.1101/2024.08.28.610209. 

PMID: 39257813.

Caveolin is a monotopic integral membrane protein, widely expressed in metazoa and responsible for constructing enigmatic membrane invaginations known as caveolae. Recently, the high-resolution structure of a purified human caveolin assembly, the CAV1-8S complex, revealed a unique organization of 11 protomers arranged in a tightly packed, radially symmetric spiral disc. One face and the outer rim of this disc are highly hydrophobic, suggesting that the complex incorporates into membranes by displacing hundreds of lipids from one leaflet. The feasibility of this unique molecular architecture and its biophysical and functional consequences are currently unknown. Using Langmuir film balance measurements, we find that CAV1-8S is highly surface active and intercalates into lipid monolayers. Molecular simulations of biomimetic bilayers support this ‘leaflet replacement’ model and reveal that while CAV1-8S effectively displaces phospholipids from one bilayer leaflet, it accumulates 40-70 cholesterol molecules into a disordered monolayer between the complex and its distal lipid leaflet. We find that CAV1-8S preferentially associates with positively curved membrane surfaces due to its influence on the conformations of distal leaflet lipids, and that these effects laterally sort lipids of the distal leaflet. Large-scale simulations of multiple caveolin assemblies confirmed their association with large, positively curved membrane morphologies, consistent with the shape of caveolae. Further, association with curved membranes regulates the exposure of caveolin residues implicated in protein-protein interactions. Altogether, the unique structure of CAV1-8S imparts unusual modes of membrane interaction with implications for membrane organization, morphology, and physiology. 

Lipid lateral diffusion: mechanisms and modulators. 

Sharma VK, Srinivasan H, Gupta J, Mitra S.

Soft Matter. 2024 Sep 24. 

doi: 10.1039/d4sm00597j. Epub ahead of print. 

PMID: 39315599.

The lateral diffusion of lipids within a membrane is of paramount importance, serving as a central mechanism in numerous physiological processes including cell signaling, membrane trafficking, protein activity regulation, and energy transduction pathways. This review offers a comprehensive overview of lateral lipid diffusion in model biomembrane systems explored through the lens of neutron scattering techniques. We examine diverse models of lateral diffusion and explore the various factors influencing this fundamental process in membrane dynamics. Additionally, we offer a thorough summary of how different membrane-active compounds, including drugs, antioxidants, stimulants, and membrane proteins, affect lipid lateral diffusion. Our analysis unveils the intricate interplay between these additives and membranes, shedding light on their dynamic interactions. We elucidate that this interaction is governed by a complex combination of multiple factors including the physical state and charge of the membrane, the concentration of additives, the molecular architecture of the compounds, and their spatial distribution within the membrane. In conclusion, we briefly discuss the future directions and areas requiring further investigation in the realm of lateral lipid diffusion, highlighting the need to study more realistic membrane systems. 

Molecules

Vinyl Ether Maleic Acid Polymers: Tunable Polymers for Self-Assembled Lipid Nanodiscs and Environments for Membrane Proteins. 

Shah MZ, Rotich NC, Okorafor EA, Oestreicher Z, Demidovich G, Eapen J, Henoch Q, Kilbey J, Prempeh G, Bates A, Page RC, Lorigan GA, Konkolewicz D. 

Biomacromolecules. 2024 Sep 16. 

doi: 10.1021/acs.biomac.4c00772. Epub ahead of print. 

PMID: 39283997.

Native lipid bilayer mimetics, including those that use amphiphilic polymers, are important for the effective study of membrane-bound peptides and proteins. Copolymers of vinyl ether monomers and maleic anhydride were developed with controlled molecular weights and hydrophobicity through reversible addition-fragmentation chain-transfer polymerization. After polymerization, the maleic anhydride units can be hydrolyzed, giving dicarboxylates. The vinyl ether and maleic anhydride copolymerized in a close to alternating manner, giving essentially alternating hydrophilic maleic acid units and hydrophobic vinyl ether units along the backbone after hydrolysis. The vinyl ether monomers and maleic acid polymers self-assembled with lipids, giving vinyl ether maleic acid lipid particles (VEMALPs) with tunable sizes controlled by either the vinyl ether hydrophobicity or the polymer molecular weight. These VEMALPs were able to support membrane-bound proteins and peptides, creating a new class of lipid bilayer mimetics. 

Conformations of membrane human immunodeficiency virus (HIV-1) envelope glycoproteins solubilized in Amphipol A18 lipid-nanodiscs. 

Zhang S, Anang S, Zhang Z, Nguyen HT, Ding H, Kappes JC, Sodroski J.

J Virol. 2024 Sep 9:e0063124. 

doi: 10.1128/jvi.00631-24. Epub ahead of print. 

PMID: 39248459.

The human immunodeficiency virus (HIV-1) envelope glycoproteins (Envs) mediate virus entry into the host cell and are targeted by neutralizing antibodies elicited by natural infection or vaccines. Detailed studies of membrane proteins like Env rely on purification procedures that maintain their natural conformation. In this study, we show that an amphipathic copolymer A18 can directly extract HIV-1 Env from a membrane without the use of detergents. A18 promotes the formation of nanodiscs that contain Env and membrane lipids. Env in A18-lipid nanodiscs largely preserves features recognized by broadly neutralizing antibodies (bNAbs) and conceals features potentially recognized by poorly neutralizing antibodies (pNAbs). Our results underscore the importance of the membrane environment to the native conformation of HIV-1 Env. Purification methods that bypass the need for detergents could be useful for future studies of HIV-1 Env structure, interaction with receptors and antibodies, and immunogenicity. 

Methods

Identification of Molecular Profile of Cell Membrane via Magnetic Plasmonic Nanoprobe. 

Wang J, Wang X, Meng F, Cong L, Shi W, Xu W, Han B, Xu S.

Anal Chem. 2024 Sep 13. 

doi: 10.1021/acs.analchem.4c01968. Epub ahead of print. 

PMID: 39268845.

Cell membranes are primarily composed of lipids, membrane proteins, and carbohydrates, and the related studies of membrane components and structures at different stages of disease development, especially membrane proteins, are of great significance. Here, we investigate the chemical signature profiles of cell membranes as biomarkers for cancer cells via label-free surface-enhanced Raman scattering (SERS). A magnetic plasmonic nanoprobe was proposed by decorating magnetic beads with silver nanoparticles, allowing self-driven cell membrane-targeted accumulation within 5 min. SERS profiles of three types of breast cells were achieved under the plasmon enhancement effect of these nanoprobes. Membrane fingerprint spectra from breast cell lines were further classified with the convolutional neural network model, which perfectly distinguished between two breast cancer subtypes. We further tested various clinical samples using this method and obtained fingerprint spectra from primary cells and frozen slices. This study presents a practical, user-friendly approach for label-free and in situ analysis of cell membranes, which can work for early tumor screening and treatment assessment for tumors reliant on the Molecular profiles of cell membranes. Additionally, this method can be applied universally to explore cell membrane components of other cells, thus assisting Human Cell Atlas. 

The retinal chromophore environment in an inward light-driven proton pump studied by solid-state NMR and hydrogen-bond network analysis. 

Pinto M, Saliminasab M, Harris A, Lazaratos M, Bondar AN, Ladizhansky V, Brown LS.

Phys Chem Chem Phys. 2024 Sep 18;26(36):24090-24108. 

doi: 10.1039/d4cp02611j. 

PMID: 39248601.

Inward proton pumping is a relatively new function for microbial rhodopsins, retinal-binding light-driven membrane proteins. So far, it has been demonstrated for two unrelated subgroups of microbial rhodopsins, xenorhodopsins and schizorhodopsins. A number of recent studies suggest unique retinal-protein interactions as being responsible for the reversed direction of proton transport in the latter group. Here, we use solid-state NMR to analyze the retinal chromophore environment and configuration in an inward proton-pumping Antarctic schizorhodopsin. Using fully ¹³C-labeled retinal, we have assigned chemical shifts for every carbon atom and, assisted by structure modelling and molecular dynamics simulations, made a comparison with well-studied outward proton pumps, identifying locations of the unique protein-chromophore interactions for this functional subclass of microbial rhodopsins. Both the NMR results and molecular dynamics simulations point to the distinctive polar environment in the proximal part of the retinal, which may result in a hydration pattern dramatically different from that of the outward proton pumps, causing the reversed proton transport. 

SAAMBE-MEM: a sequence-based method for predicting binding free energy change upon mutation in membrane protein-protein complexes. 

Rimal P, Panday SK, Xu W, Peng Y, Alexov E.

Bioinformatics. 2024 Sep 2;40(9):btae544. 

doi: 10.1093/bioinformatics/btae544. 

PMID: 39240325.

Motivation: Mutations in protein-protein interactions can affect the corresponding complexes, impacting function and potentially leading to disease. Given the abundance of membrane proteins, it is crucial to assess the impact of mutations on the binding affinity of these proteins. Although several methods exist to predict the binding free energy change due to mutations in protein-protein complexes, most require structural information of the protein complex and are primarily trained on the SKEMPI database, which is composed mainly of soluble proteins. 

Results: A novel sequence-based method (SAAMBE-MEM) for predicting binding free energy changes (ΔΔG) in membrane protein-protein complexes due to mutations has been developed. This method utilized the MPAD database, which contains binding affinities for wild-type and mutant membrane protein complexes. A machine learning model was developed to predict ΔΔG by leveraging features such as amino acid indices and position-specific scoring matrices (PSSM). Through extensive dataset curation and feature extraction, SAAMBE-MEM was trained and validated using the XGBoost regression algorithm. The optimal feature set, including PSSM-related features, achieved a Pearson correlation coefficient of 0.64, outperforming existing methods trained on the SKEMPI database. Furthermore, it was demonstrated that SAAMBE-MEM performs much better when utilizing evolution-based features in contrast to physicochemical features. 

Availability and implementation: The method is accessible via a web server and standalone code at http://compbio.clemson.edu/SAAMBE-MEM/. The cleaned MPAD database is available at the website. 

Microbio

TolC and EmrA1 contribute to Francisella novicida multidrug resistance and modulation of host cell death. 

Kopping EJ, Benziger PT, Thanassi DG.

J Bacteriol. 2024 Sep 19;206(9):e0024624. 

doi: 10.1128/jb.00246-24. Epub 2024 Aug 28. 

PMID: 39194223.

Francisella tularensis is a Gram-negative intracellular bacterial pathogen and causative agent of tularemia. We previously identified the outer membrane channel protein TolC as contributing to antimicrobial resistance and subversion of host responses by F. tularensis. To advance understanding of TolC function in Francisella and to identify components that might work together with TolC, we took advantage of a transposon mutant library in F. novicida, a model species that causes a tularemia-like disease in mice. Our findings identify TolC and the membrane fusion protein EmrA1 as important for both antimicrobial resistance and suppression of macrophage cell death. This study also revealed differences in cell death pathways triggered by F. novicida versus F. tularensis infection that may relate to differences in virulence. 

Roles of Pseudomonas aeruginosa siderophores in interaction with prokaryotic and eukaryotic organisms. 

Jeong GJ, Khan F, Tabassum N, Jo DM, Jung WK, Kim YM.

Res Microbiol. 2024 Sep-Oct;175(7):104211. 

doi: 10.1016/j.resmic.2024.104211. Epub 2024 May 9. 

PMID: 38734157.

Pseudomonas aeruginosa is an opportunistic pathogen that produces two types of siderophores, pyoverdine and pyochelin, that play pivotal roles in iron scavenging from the environment and host cells. P. aeruginosa siderophores can serve as virulence factors and perform various functions. Several bacterial and fungal species are likely to interact with P. aeruginosa due to its ubiquity in soil and water as well as its potential to cause infections in plants, animals, and humans. Siderophores produced by P. aeruginosa play critical roles in iron scavenging for prokaryotic species (bacteria) and eukaryotic hosts (fungi, animals, insects, invertebrates, and plants) as well. This review provides a comprehensive discussion of the role of P. aeruginosa siderophores in interaction with prokaryotes and eukaryotes as well as their underlying mechanisms of action. The evolutionary relationship between P. aeruginosa siderophore recognition receptors, such as FpvA, FpvB, and FptA, and those of other bacterial species has also been investigated. 

Miscellaneous

Scientists successfully ‘nuke asteroid’ – in a lab mock-up. 

O’Callaghan J.

Nature. 2024 Sep 23. 

doi: 10.1038/d41586-024-03128-4. Epub ahead of print. 

PMID: 39313651.

A blast of X-rays from a nuclear explosion should be enough to save Earth from an incoming asteroid a first-of-its-kind experiment shows. Researchers recreated the scenario in miniature firing X-rays at two 12-millimetre mock asteroids made of quartz and silica. In just 20 millionths of a second the samples were accelerated to high speeds as the X-rays vaporized their surface creating a thrust as gas expanded away from them. The results “showed some really amazing direct experimental evidence for how effective this technique can be” says physicist Dawn Graninger.

MolPlay: Democratizing Interactive Molecular Simulations and Analyses with a Portable, Turnkey Platform. 

Baaden M.

J Phys Chem B. 2024 Sep 26;128(38):9132-9142. 

doi: 10.1021/acs.jpcb.4c04712. Epub 2024 Sep 17. 

PMID: 39287415.

Computer-based tools for visualizing and manipulating molecular structures in real-time hold immense potential for accelerating research and improving education, but are only used to a limited extent. This paper explores the possibilities of these powerful techniques and presents a classification of common interactive modeling tasks, such as assembly, deformation, sampling of rare events, along with relevant use cases, especially for the study of membranes and membrane proteins. I introduce MolPlay─a platform that provides a ready-to-use software environment with a curated set of hands-on examples to democratize access to interactive molecular simulations and analyses (IMSA). These research tools allow researchers to visualize, manipulate, and study digital models of molecules in real-time and can be started directly from a small, portable storage device. The portable, self-contained nature of MolPlay enables versatile deployment scenarios ranging from outreach to teaching in computer laboratories to facilitating the distribution of research software. Initial tests at an international workshop have shown that MolPlay appeals to different target groups and lowers the access barriers to IMSA. By consolidating more than a decade of expertise into one accessible platform, MolPlay represents a significant step toward broader adoption of these underutilized but powerful computational techniques in education and research. 

Red light, green light: flickering fluorophores reveal biochemistry in cells. 

Katsnelson A.

Nature. 2024 Sep 12. 

doi: 10.1038/d41586-024-02964-8. Epub ahead of print. 

PMID: 39266732.

Proteins rarely act alone — they do their jobs by interacting with other proteins. Conventionally researchers have studied those complexes in test tubes but a new approach called PAPA-fSMT enables analysis in the cell itself. The method exploits the observation that some seemingly dead fluorescent molecules can be selectively reactivated by light of a different wavelength — if the two fluorophores are close together in space.

and, of course …

The 2024 Ig Nobel Prize Winners

The 2024 Ig Nobel Prizes were awarded at the 34th First Annual Ig Nobel Prize ceremony on Thursday evening September 12 2024 at MIT.

PEACE PRIZE [USA]
B.F. Skinner, for experiments to see the feasibility of housing live pigeons inside missiles to guide the flight paths of the missiles.

BOTANY PRIZE [GERMANY, BRAZIL, USA]
Jacob White and Felipe Yamashita, for finding evidence that some real plants imitate the shapes of neighboring artificial plastic plants.

ANATOMY  PRIZE [FRANCE, CHILE]
Marjolaine Willems, Quentin Hennocq, Sara Tunon de Lara, Nicolas Kogane, Vincent Fleury, Romy Rayssiguier, Juan José Cortés Santander, Roberto Requena, Julien Stirnemann, and Roman Hossein Khonsari, for studying whether the hair on the heads of most people in the northern hemisphere swirls in the same direction (clockwise or counter-clockwise?) as hair on the heads of most people in the southern hemisphere.

MEDICINE PRIZE [SWITZERLAND, GERMANY, BELGIUM]
Lieven A. Schenk, Tahmine Fadai, and Christian Büchel, for demonstrating that fake medicine that causes painful side-effects can be more effective than fake medicine that does not cause painful side-effects.

PHYSICS PRIZE [USA]
James C. Liao, for demonstrating and explaining the swimming abilities of a dead trout.

PHYSIOLOGY PRIZE [JAPAN, USA]
Ryo Okabe, Toyofumi F. Chen-Yoshikawa, Yosuke Yoneyama, Yuhei Yokoyama, Satona Tanaka, Akihiko Yoshizawa, Wendy L. Thompson, Gokul Kannan, Eiji Kobayashi, Hiroshi Date, and Takanori Takebe, for discovering that many mammals are capable of breathing through their anus.

PROBABILITY PRIZE [THE NETHERLANDS, SWITZERLAND, BELGIUM, FRANCE, GERMANY, HUNGARY, CZECH REPUBLIC]
František Bartoš, Eric-Jan Wagenmakers, Alexandra Sarafoglou, Henrik Godmann, and many colleagues, for showing, both in theory and by 350,757 experiments, that when you flip a coin, it tends to land on the same side as it started.

CHEMISTRY PRIZE [THE NETHERLANDS, FRANCE]
Tess Heeremans, Antoine Deblais, Daniel Bonn, and Sander Woutersen, for using chromatography to separate drunk and sober worms.

DEMOGRAPHY PRIZE [AUSTRALIA, UK]
Saul Justin Newman, for detective work to discover that many of the people famous for having the longest lives lived in places that had lousy birth-and-death recordkeeping.