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20241028_membrane digest 1/2

MP

Dissected antiporter modules establish minimal proton-conduction elements of the respiratory complex I. 

Beghiah A, Saura P, Badolato S, Kim H, Zipf J, Auman D, Gamiz-Hernandez AP, Berg J, Kemp G, Kaila VRI.

Nat Commun. 2024 Oct 22;15(1):9098. 

doi: 10.1038/s41467-024-53194-5. 

PMID: 39438463.

Minimal proton-conducting membrane modules using bacterial Complex I reconstituted in proteoliposomes => isolated antiporter-like modules contain all elements necessary for proton conduction. 

Proton conduction is controlled by conformational changes of buried ion-pairs and modulated by bulky residues along the proton channels. 

Direct evidence that individual antiporter modules are responsible for proton transport + reveal electrostatic and conformational coupling mechanisms essential for Complex I’s energy transduction.

 

The ultra-high affinity transport proteins of ubiquitous marine bacteria. 

Clifton BE, Alcolombri U, Uechi GI, Jackson CJ, Laurino P.

Nature. 2024 Oct;634(8034):721-728. 

doi: 10.1038/s41586-024-07924-w. Epub 2024 Sep 11. 

PMID: 39261732.

SAR11 bacteria* dominate the ocean’s surface and play crucial roles in global nutrient cycles, relying on specialized solute-binding proteins to grow in nutrient-poor waters. 

Here: Experimental map of the functions of all solute-binding proteins in a SAR11 bacterium => exceptionally high affinity and specificity for substrates. 

Identification of new carbon sources for SAR11 + improvement of predictions of where and how these bacteria absorb nutrients across the ocean.

 

* The Pelagibacterales are an order in the Alphaproteobacteria composed of free-living marine bacteria that make up roughly one in three cells at the ocean’s surface. Overall members of the Pelagibacterales are estimated to make up between a quarter and a half of all prokaryotic cells in the ocean. Initially this taxon was known solely by metagenomic data and was known as the SAR11 clade. (source: Wikipedia)

 

A highly conserved SusCD transporter determines the import and species-specific antagonism of Bacteroides ubiquitin homologues. 

Tong M, Xu J, Li W, Jiang K, Yang Y, Chen Z, Jiao X, Meng X, Wang M, Hong J, Long H, Liu SJ, Lim B, Gao X.

Nat Commun. 2024 Oct 10;15(1):8794. 

doi: 10.1038/s41467-024-53149-w. 

PMID: 39389974.

Bacteroides fragilis produces an antimicrobial protein, BfUbb, which selectively targets and kills other B. fragilis strains by binding to a critical enzyme within their periplasm. 

Transport of BfUbb is mediated by ButCD (widely distributed across Bacteroides species but varies in sequence). 

CryoEM structure of the BfUbb-ButCD => distinctive features of the ButCD transporter essential for BfUbb recognition and selective import. 

Animal experiments => BfUbb eliminates pathogenic B. fragilis strains in the gut. 

 

Arabidopsis HAK5 under low K+ availability operates as PMF powered high-affinity K+ transporter. 

Maierhofer T, Scherzer S, Carpaneto A, Müller TD, Pardo JM, Hänelt I, Geiger D, Hedrich R.

Nat Commun. 2024 Oct 3;15(1):8558. 

doi: 10.1038/s41467-024-52963-6. 

PMID: 39362862.

Plants have evolved to absorb potassium (K+) even in low-K+ environments, primarily through the AKT1 channel and high-affinity transporter HAK5. 

AKT1 functions under moderate K+ levels. 

HAK5 becomes critical as K+ availability drops, actively transporting K+ by coupling it with proton flow. 

Here: authors show that HAK5 only activates under low-K+ conditions and identify the amino acid Y450 as crucial for HAK5’s high K+ affinity. 

 

Substrate engagement by the intramembrane metalloprotease SpoIVFB. 

Orlando MA, Pouillon HJT, Mandal S, Kroos L, Orlando BJ.

Nat Commun. 2024 Oct 17;15(1):8276. 

doi: 10.1038/s41467-024-52634-6. 

PMID: 39419996.

S2P = intramembrane metalloproteases which substrate engagement and peptide hydrolysis mechanisms have been unclear. 

Here: cryo-EM structure of the S2P protease SpoIVFB from Bacillus subtilis bound to its substrate Pro-σK.

  • SpoIVFB uses a β-sheet augmentation mechanism to position Pro-σK at its active site. 
  • highlight of the important interactions between Pro-σK and SpoIVFB’s interdomain linker. 
  • Structure shows a potential route for water to access SpoIVFB’s membrane-embedded active site =>  lipids might help in capturing substrates.

 

Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition. 

Maharjan R, Zhang Z, Klenotic PA, Gregor WD, Tringides ML, Cui M, Purdy GE, Yu EW.

PLoS Biol. 2024 Oct 18;22(10):e3002874. doi: 10.1371/journal.pbio.3002874. Epub ahead of print. PMID: 39423221.

 

Cryo-EM structures of MmpL4 and MmpL5, transporters involved in iron homeostasis, in M. smegmatis. 

=> potential pathway for siderophore translocation.

 

Efflux pumps mediate changes to fundamental bacterial physiology via membrane potential. 

Whittle EE, Orababa O, Osgerby A, Siasat P, Element SJ, Blair JMA, Overton TW.

mBio. 2024 Oct 16;15(10):e0237024. 

doi: 10.1128/mbio.02370-24. Epub 2024 Sep 9. 

PMID: 39248573.

Inactivating AcrB alters bacterial physiology, notably slowing entry into the stationary phase and increasing membrane potential. The lack of AcrB shifts energy metabolism and may increase antibiotic uptake by extending the growth phase when cells are more susceptible. 

Membrane hyperpolarization could also boost the production of reactive species, enhancing antibiotic efficacy.

 

Membranes

Hasani M, Esch K, Zieske K. Controlled Protein-Membrane Interactions Modulate Self-Organization of Min Protein Patterns. 

Angew Chem Int Ed Engl. 2024 Oct 14;63(42):e202405046. 

doi: 10.1002/anie.202405046. Epub 2024 Sep 12. 

PMID: 39023015.

Study exploring how simple biophysical parameters, specifically changes in membrane affinity, can regulate these protein patterns, particularly focusing on Min proteins in E. coli. 

=> identification of a range of pattern phenotypes: waves and snowflake-like structures, influenced by the density of protein-membrane linkers. 

=> the membrane charge shapes the snowflake-like patterns, highlighting the role of membrane interactions in pattern formation. 

=> Mechanism for cells to dynamically tune and switch protein patterns ?

 

Insight into the outer membrane asymmetry of P. aeruginosa and the role of MlaA in modulating the lipidic composition, mechanical, biophysical, and functional membrane properties of the cell envelope. 

Kaur M, Mozaheb N, Paiva TO, Herent M-F, Goormaghtigh F, Paquot A, Terrasi R, Mignolet E, Décout J-L, Lorent JH, Larondelle Y, Muccioli GG, Quetin-Leclercq J, Dufrêne YF, Mingeot-Leclercq M-P.

Microbiol Spectr. 2024 Oct 7:e0148424. 

doi: 10.1128/spectrum.01484-24. Epub ahead of print. 

PMID: 39373473.

In Gram-negative bacteria, OM maintains asymmetry with LPS the outer leaflet and glycerophospholipids (GPLs) in the inner leaflet thanks to the Mla system. 

Here: examination how P. aeruginosa responds to the deletion of mlaA and investigation of the changes in membrane lipid composition, biophysical properties, and antibiotic susceptibility. 

∆mlaA => increase in GPLs and a decrease in LPS + modifications to lipid A structures => impact on the overall stiffness and fluidity of the OM. 

Altered lipid composition => enhances membrane vesiculation without affecting permeability, while treatment with a specific aminoglycoside restores some characteristics of the wild-type strain.

 

Microfluidic technologies for lipid vesicle generation. 

Cheng Y, Hay CD, Mahuttanatan SM, Hindley JW, Ces O, Elani Y.

Lab Chip. 2024 Oct 9;24(20):4679-4716. 

doi: 10.1039/d4lc00380b. 

PMID: 39323383.

Encapsulating materials in lipid vesicles offers significant potential for applications in drug delivery, biotechnology, and synthetic biology. 

Lipid nanoparticles <100 nm enhance drug delivery (improved pharmacokinetics and minimized off-target effects).

Vesicles > 1 μm serve as model membranes and platforms for exploring life’s origins. 

Advanced microfluidic methods have emerged as a leading technology for their controlled production => they provide precise size control, high encapsulation efficiency, and customizable membrane properties. 

Here: review on recent advancements in microfluidic lipid vesicle generation.

 

 

Molecules

Polymer nanodiscs support the functional extraction of an artificial transmembrane cytochrome. 

Hardy BJ, Ford HC, Rudin M, Anderson JLR, Curnow P.

Biochim Biophys Acta Biomembr. 2024 Oct 15;1867(1):184392. 

doi: 10.1016/j.bbamem.2024.184392. Epub ahead of print. 

PMID: 39414100.

”Polymer nanodiscs” to isolate a computationally-designed de novo membrane cytochrome named CytbX. 

=> CyclAPols can efficiently extract CytbX directly from biomembranes and are compatible with downstream purification and biophysical characterisation. 

=> CyclAPol-solubilised CytbX is well-folded and highly robust with properties that are essentially identical to those observed for the same protein in a detergent micelle. 

=> Electron transfer to CytbX from a diffusive flavoprotein is substantially faster in micelles than in the nanodisc system.

 

💪CyclAPols🤘

 

Methods

Stability vs flexibility: reshaping monolayer and bilayer archaeal membranes in silico

Miguel Amaral, Felix Frey, Xiuyun Jiang, Buzz Baum, Anđela Šarić

bioRxiv 2024.10.18.619072; 

doi: https://doi.org/10.1101/2024.10.18.619072

Bacteria and eukaryotes use single-headed lipids to form flexible bilayers, while archaea often utilize both bilayer and double-headed bolalipids to survive in extreme environments. 

Here: minimal computational model for bolalipid membranes. 

Flexible bolalipid membranes can adopt U-shaped conformations (similar to bilayer membranes) allowing for higher curvature, while stiffer bolalipids tend to form stable liquid membranes that are less adaptable and prone to pore formation. 

Small fraction of bilayer lipids into a bolalipid membrane => combination of fluidity, stability at elevated temperatures, and the flexibility needed for reshaping without leakage.

 

 

Microbio

Characterisation of Pseudomonas aeruginosa’s metal-responsive TonB-dependent transporters

Manon Ferry, Hortense Ferriz, Connor Sharp, Christos Paschalidis, Emmanuel Boutant, Isabelle J. Schalk, Olivier Cunrath

bioRxiv 2024.10.14.618150; 

doi: https://doi.org/10.1101/2024.10.14.618150 

P. aeruginosa => various TBDTs to acquire nutrients like iron-siderophore complexes and adapt to different environments, yet many of these transporters remain poorly understood. 

Here: fluorescent reporter plasmids to investigate the promoter activity of TBDTs. 

=> TBDTs classified into distinct metal-responsive groups based on their stress response behavior, providing insights into their functional roles. 

=> reporter constructs proved effective for detecting siderophores.

=> single-cell analysis during coculture with Klebsiella pneumoniae showed homogeneous expression of key TBDTs in P. aeruginosa. 

 

 

Miscellaneous

Prédiction de structures biomoléculaires complexes par AlphaFold 3.

Taly A, Verger A.

 Med Sci (Paris). 2024 Oct;40(10):725-727. French. 

doi: 10.1051/medsci/2024124. Epub 2024 Oct 25. 

PMID: 39450957.

A must-read overview on the must-use-with-care-Nobel-prized AF3 by Alexis Verger and Antoine Taly.

 

The Israel-Hamas conflict one year on: researcher resilience in the face of war. 

Glausiusz J.

Nature. 2024 Oct;634(8033):501-503. 

doi: 10.1038/d41586-024-03263-y. 

PMID: 39375570.

A year on from the 7 October attacks by Hamas on Israel and the start of the war in Gaza scientists on both sides of the border are searching for ways forward. Many are facing the devastation of losing livelihoods homes loved ones and colleagues. All 19 universities and community colleges in Gaza have been destroyed or damaged. “The loss of talent enrages and saddens me so much” says an anonymous environmental scientist in Israel who is working to help two Gaza master’s students to flee. “I know what these kids would [accomplish] if there were different circumstances.”
 

 

Microphysical interactions determine the effectiveness of solar radiation modification via stratospheric solid particle injection. 

Vattioni, S.,  Käslin, S. K.,  Dykema, J. A.,  Beiping, L., Sukhodolov, T.,  Sedlacek, J., et al. (2024).

Geophysical Research Letters,  51, e2024GL110575. https://doi.org/10.1029/2024GL110575

A mere 5 million tonnes of diamond dust sprinkled in the skies each year could cool the climate by 1.6 ℃, finds an eye-popping comparison of different geoengineering ideas. The plan would avoid some of the downsides of other materials being mooted for ‘stratospheric aerosol injection’. For example, sulfur dioxide — which has a natural cooling effect when spewed by volcanic eruptions — risks acid rain and damage to the ozone layer. But synthetic diamond would cost something like US$175 trillion if deployed from 2035 to 2100, whereas sulfur is widely available and very cheap.

 

How much energy does it take to make a baby? Researchers are rethinking what they know

https://www.nature.com/articles/d41586-024-03402-5

Evolutionary biologist Dustin Marshall thinks that researchers might have vastly underestimated the energy it takes to reproduce. Many influential mathematical models of species’ energy demands estimate only the ‘direct’ energy cost to produce young — the energy invested and stored in the offspring. This ignores a big energy-spend by mothers, the ‘indirect costs’ of making and carrying a baby. Marshall’s team has even found that the indirect costs might greatly exceed the direct ones, particularly in mammals. These findings could influence theories about aspects of animal lifestyles and improve predictions about how animals will respond to climate change, Marshall says.

 

Inducing novel endosymbioses by implanting bacteria in fungi. 

Giger GH, Ernst C, Richter I, Gassler T, Field CM, Sintsova A, Kiefer P, Gäbelein CG, Guillaume-Gentil O, Scherlach K, Bortfeld-Miller M, Zambelli T, Sunagawa S, Künzler M, Hertweck C, Vorholt JA.

Nature. 2024 Oct 2. 

doi: 10.1038/s41586-024-08010-x. Epub ahead of print. 

PMID: 39358514.

With a tiny hollow needle and a bicycle pump scientists have successfully kick-started an artificial endosymbiotic relationship by implanting bacteria into a fungus cell. These relationships in which a microbial partner lives harmoniously within the cells of another organism are thought to be what sparked the evolution of complex life. The systems could help researchers to understand how cell structures such as mitochondria and chloroplasts emerged more than a billion years ago. Researchers recreated a natural symbiosis by implanting the bacterium Mycetohabitans rhizoxinica into the fungi Rhizopus microsporus. When spores germinated bacteria were also present in the cells of the next generation of fungi showing that the endosymbiosis could be passed onto offspring.

 

 

GoToCloud optimization of cloud computing environment for accelerating cryo-EM structure-based drug design. 

Moriya T, Yamada Y, Yamamoto M, Senda T.

Commun Biol. 2024 Oct 14;7(1):1320. 

doi: 10.1038/s42003-024-07031-6. 

PMID: 39402335.

Achieving the required throughput for cryoEM structure-based drug design (SBDD) is a challenge, largely due to data analysis bottlenecks. 

“GoToCloud” platform = cloud-computing solution for advanced data analysis and management in Cryo-EM, enabling the optimization of computing resources. 

Benchmark tests indicate that parallel computing settings, including the choice of hardware and target resolution, significantly affect processing time and cost efficiency.

 

The early days of peer review: five insights from historical reports. 

Adam D.

Nature. 2024 Oct;634(8035):761-762. 

doi: 10.1038/d41586-024-03287-4. 

PMID: 39406846.

A crop of referee reports from the Royal Society’s archive reveal discussions about cutting printing costs, reviewer holidays and even editing images.