MP

OmpA controls order in the outer membrane and shares the mechanical load. 

Benn G, Borrelli C, Prakaash D, Johnson ANT, Fideli VA, Starr T, Fitzmaurice D, Combs AN, Wühr M, Rojas ER, Khalid S, Hoogenboom BW, Silhavy TJ.

Proc Natl Acad Sci U S A. 2024 Dec 10;121(50):e2416426121. 

doi: 10.1073/pnas.2416426121. Epub 2024 Dec 4. 

PMID: 39630873.

Both the β-barrel and cell wall-binding domains of OmpA are essential for strengthening the cell envelope and maintaining the OM’s permeability barrier. By integrating the compressive properties of the OM with the tensile strength of the CW, OmpA creates a mechanically robust composite critical for bacterial survival.

Update on the structure and function of Candida albicans drug efflux protein, Cdr1. 

Ibe C, Pohl CH.

Fungal Genet Biol. 2024 Dec;175:103938. 

doi: 10.1016/j.fgb.2024.103938. Epub 2024 Oct 30. 

PMID: 39486613.

Candida albicans = significant human pathogenic yeast, can develop resistance to antifungal agents like azoles through efflux via ABC T such as Cdr1. 

Here: review synthesizing structure, binding mechanisms, function, and regulation.

Identification of efflux pump inhibitors for Pseudomonas aeruginosa MexAB-OprM via ligand-based pharmacophores, 2D-QSAR, molecular docking, and molecular dynamics approaches. 

Phan TV, Nguyen VT, Le MT, Nguyen BGD, Vu TT, Thai KM.

Mol Divers. 2024 Oct;28(5):3295-3311. 

doi: 10.1007/s11030-023-10758-9. Epub 2023 Nov 3. 

PMID: 37919619.

Identification of 611 potential EPIs from MexAB-OprM (EP from P. aeruginosa) through virtual screening, docking, and molecular dynamics analysis, highlighting two strong candidates with favorable binding affinities, pharmacokinetics, and safety profiles for potential oral drug development.

An anomalous abundance of tryptophan residues in ceramide synthases based on analysis of all membrane proteins in the Swiss-Prot database. 

Mestre B, Zelnik ID, Izrailov S, Dingjan T, Lvovsky G, Fidel L, Ben-Dor S, Futerman AH.

J Biol Chem. 2024 Dec 7:108053. 

doi: 10.1016/j.jbc.2024.108053. Epub ahead of print. 

PMID: 39653242.

The distribution of Trp in MPs is higher than in soluble proteins => role in anchoring proteins to membranes ? However levels are lower than previously reported. 

Ceramide synthase = unusually high Trp content, with residues asymmetrically distributed towards the lumenal side, critical for its activity, expression, and glycosylation. 

Mutations of conserved Trp residues significantly affect CerS function => Trp is vital for both membrane anchoring and the functional integrity of transmembrane proteins.

Membranes

Established and emerging players in phospholipid scrambling: A structural perspective. 

Sebinelli HG, Syska C, Čopič A, Lenoir G.

Biochimie. 2024 Dec;227(Pt B):111-122. 

doi: 10.1016/j.biochi.2024.09.008. Epub 2024 Sep 18. 

PMID: 39304020.

Some lipid scramblases facilitate rapid transbilayer lipid movement during processes like apoptosis and blood clotting, while others contribute to autophagosomal membrane synthesis. 

Here: Review on the advances in structural studies and molecular simulations that have clarified scrambling mechanisms and pathways (some scramblases combine lipid transport with, for instance, ion channel activity).

Structural insights into the force-transducing mechanism of a motor-stator complex important for bacterial outer membrane lipid homeostasis

Jiang Yeow, Chee Geng Chia, Nadege Zi-Lin Lim, and Shu-Sin Chng

bioRxiv posted 29 November 2024 doi:10.1101/2024.11.27.625625

Gram-negative bacteria rely on the Tol-Pal complex to maintain OM lipid homeostasis, using the TolQR motor-stator to harness pmf for activating processes at the OM. 

Here: cryo-EM structure of the TolQRA complex structure in two states 

=> interactions between TolA and the TolQ5R2 sub-complex, with the states connected by rotation of the TolQ pentamer. 

=> proposed model: proton passage induces rotary movement in the complex, enabling force transduction across the cell envelope.

The pleomorphic cholesterol sensing motifs of transmembrane proteins. 

Barrantes FJ.

Chem Phys Lipids. 2024 Nov 29;266:105460. 

doi: 10.1016/j.chemphyslip.2024.105460. Epub ahead of print. 

PMID: 39615777.

Evolution => interplay between sterols and MPs. 

Primitive bacteria utilized basic sterol interactions, while eukaryotic systems evolved complex cholesterol-binding sites requiring intricate 3D protein structures for precise binding. 

Here: review highlighting cholesterol-MP interactions in key processes (neurotransmission, hormone signaling, and cancer)

Drivers of Morphogenesis: Curvature Sensor Self-Assembly at the Membrane. 

Curtis BN, Gladfelter AS.

Cold Spring Harb Perspect Biol. 2024 Dec 2;16(12):a041528. 

doi: 10.1101/cshperspect.a041528. 

PMID: 38697653.

Review exploring how nanometer-scale curvature-sensing proteins detect micrometer-scale membrane features through electrostatic and hydrophobic interactions, influenced by lipid charge, packing, and curvature directionality.

BioDolphin as a comprehensive database of lipid-protein binding interactions. 

Yang LY, Ping K, Luo Y, McShan AC.

Commun Chem. 2024 Dec 4;7(1):288. 

doi: 10.1038/s42004-024-01384-z. 

PMID: 39633021.

Comprehensive data on these Lipid-protein interactions is lacking. 

Here: BioDolphin = curated database with over 127,000 annotated lipid-protein interactions => binding affinities, classifications, and interactive 3D visualization of complexes. 

Bioinspired adaptive lipid-integrated bilayer coating for enhancing dynamic water retention in hydrogel-based flexible sensors. 

Bai M, Chen Y, Zhu L, Li Y, Ma T, Li Y, Qin M, Wang W, Cao Y, Xue B.

Nat Commun. 2024 Dec 4;15(1):10569. 

doi: 10.1038/s41467-024-54879-7. 

PMID: 39632850.

Hydrogel-based flexible sensors are prone to water evaporation.

Here: developpement of an adaptive lipid-integrated bilayer coating using lipid layers and amphiphilic molecules to anchor and protect hydrogels while allowing spare lipids to combat dehydration during deformation. 

=> retains water without compromising flexibility or conductivity + significantly improvement of sensor performance under heat, deformation, and long-term use.

Microdomains heterogeneity in the thylakoid membrane proteins visualized by super-resolution microscopy. 

Kaňa R, Šedivá B, Prášil O.

Photosynthetica. 2023 Dec 18;61(4):483-491. 

doi: 10.32615/ps.2023.043. 

PMID: 39649485.

Research into thylakoid membrane protein heterogeneity has uncovered microdomains in cyanobacteria. 

Here: using super-resolution Airyscan microscopy, areas rich in PS I were identified within inner thylakoid membrane rings, along with similar mobility dynamics for PS II and phycobilisomes, challenging prior models of differing mobility.

Constant-pH MD Simulations of Lipids

Marius F.W. Trollmann, Paolo Rossetti, and Rainer A Böckmann

bioRxiv posted 9 December 2024 

doi:10.1101/2024.12.06.627182

Constant pH MS (CpHMD) = powerful method for studying the pH-dependent behavior of biological systems. This chapter demonstrates how CpHMD can be applied to investigate Cationic Ionizable Lipids in lipid nanoparticles (LNPs), which are crucial for drug delivery and were instrumental in mRNA vaccine development during the SARS-CoV-2 pandemic. 

Cell Membranes Sustain Phospholipid Imbalance Via Cholesterol Asymmetry

Milka Doktorova, Jessica L Symons, Xiaoxuan Zhang, Hong-Yin Wang, Jan Schlegel, Joseph H Lorent, Frederick A Heberle, Erdinc Sezgin, Edward Lyman, Kandice R Levental, and Ilya Levental

bioRxiv posted 9 December 2024 

doi:10.1101/2023.07.30.551157

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. 2025 Jan;1867(1):184392. 

doi: 10.1016/j.bbamem.2024.184392. Epub 2024 Oct 15. 

PMID: 39414100.

Polymer nanodiscs, like CyclAPols (💪), provide a native lipid environment for studying MPs.

Here: CyclAPols successfully extracted CytbX from biomembranes, maintaining its folding and robustness, comparable to its properties in detergent micelles. Electron transfer to CytbX faster in micelles.

Methods

De novo non-compartmentalized microorganism for directed evolution of nanobodies

Donglian Wu, Huiping He, Ruyu Xi, Simin Xia, and Xi Chen

bioRxiv posted 28 November 2024 

doi:10.1101/2024.11.27.625622

“Syn-phage” = synthetic microorganism designed as a mimic of natural phages, capable of evolving nanobodies with enhanced properties. 

Syn-phage integrates genetic and phenotypic materials and can amplify within an E. coli host => evolution of Nb with improved affinity. 

Time-resolved cryo-EM (TRCEM) sample preparation using a PDMS-based microfluidic chip assembly

Xiangsong Feng and Joachim Frank

bioRxiv posted 9 December 2024 doi:10.1101/2024.12.08.627437

This study introduces a time-resolved cryo-EM (TRCEM) setup that combines a PDMS-based microfluidic chip assembly to capture biomolecular reactions (10–1000 ms time frame), crucial for studying pre-equilibrium intermediates. 

Potential for exploring structural and kinetic details of various molecular processes : demonstration with ribosome recycling mediated by HflX.

Best practice mass photometry: A guide to optimal single molecule mass measurement

Jiri Kratochvil, Raman van Wee, Dan Loewenthal, Jan Christoph Thiele, Jack Bardzil, Kishwar Iqbal, Stephen Thorpe, and Philipp Kukura

bioRxiv posted 4 December 2024 

doi:10.1101/2024.12.03.624087

MP for MP ? no det

Membrane transport engineering for efficient yeast biomanufacturing. 

Li XY, Zhou MH, Zeng DW, Zhu YF, Zhang FL, Liao S, Fan YC, Zhao XQ, Zhang L, Bai FW.

Bioresour Technol. 2024 Dec 5;418:131890. 

doi: 10.1016/j.biortech.2024.131890. Epub ahead of print. 

PMID: 39644936.

Yeast strains are valuable for biomanufacturing, but challenges like low yields and high costs persist despite optimizations. 

Membrane transport engineering (modification of transporters and membrane properties) => promise for improving production by enhancing the transport of metabolites and optimizing membrane lipid bilayers. 

Microbio

Efflux pumps: gatekeepers of antibiotic resistance in Staphylococcus aureus biofilms. 

Sinha S, Aggarwal S, Singh DV.

Microb Cell. 2024 Nov 11;11:368-377. 

doi: 10.15698/mic2024.11.839. 

PMID: 39568862.

Review highlighting the complex interplay between efflux pumps, resistance, and biofilms, offering insights to guide the development of novel therapies targeting these mechanisms in S. aureus infections.

Multidrug efflux pumps of Pseudomonas aeruginosa show selectivity for their natural substrates

Front. Microbiol. Sec. Antimicrobials, Resistance and Chemotherapy

Volume 15 – 2024 | doi: 10.3389/fmicb.2024.1512472

Metabolomic => identification of 210 efflux pump substrates (signaling molecules, metabolic by-products, oxidized fatty acids, …) revealing that Mex pumps have specific roles in extruding these compounds. 

These insights into natural substrates provide a foundation for developing competitive inhibitors to combat antibiotic resistance in P. aeruginosa.

Microplastics as a novel facilitator for antimicrobial resistance: Effects of concentration, composition, and size on Escherichia coli multidrug resistance

Neila Gross, Johnathan Muhvich, Carly Ching, Bridget Gomez, Yanina Nahum, Evan Horvath, Muhammad H Zaman.

bioRxiv 2024.08.01.606221; 

doi: https://doi.org/10.1101/2024.08.01.606221

Study highlighting the relationship between microplastics and the rise of drug-resistant bacteria. 

Microplastics promote antibiotic resistance more effectively than control substrates like glass due to their hydrophobicity, adsorption properties, and surface chemistry, facilitating biofilm formation. 

Bacteria cultured with microplastics develop enhanced biofilm-forming abilities even after microplastics removal.

Bacterial peptidoglycan recycling. 

Gilmore MC, Cava F.

Trends Microbiol. 2024 Nov 28:S0966-842X(24)00286-5. 

doi: 10.1016/j.tim.2024.11.004. Epub ahead of print. 

PMID: 39613687.

During growth and division, the bacterial cell wall is remodeled, => liberation PG fragments which are typically reinternalized and recycled. 

Here: review how bacteria transport and recycle the components of their PG.

Miscellaneous 

Breaking bad

The New York Times

Criminal groups in Mexico are recruiting chemistry students to upgrade their production of the drug fentanyl. Crackdowns on the trade in precursors from China have put the gangs under pressure, and they hope to develop the ability to produce these raw materials in-house. In some cases, students enrol in chemistry classes to gain skills relevant to the illicit trade. “Sometimes when I am teaching them synthesis of pharmaceutical drugs, they openly ask me, ‘Hey, professor, when are you teaching us how to synthesize cocaine and other things?’” says one anonymous chemist.

Wuhan lab samples hold no close relatives to virus behind COVID

Mallapaty S.

Nature. 2024 Dec;636(8043):531-532. 

doi: 10.1038/d41586-024-03982-2. 

PMID: 39643624.

Shi Zhengli, the virologist at the centre of claims that the virus that causes COVID-19 escaped from a laboratory in Wuhan, has presented data on 56 whole genomes of bat coronaviruses, as well as some partial sequences, stored in her lab’s freezers. Her analysis reports that none of those viruses are the most recent ancestors of the virus SARS-CoV-2.

More-powerful AI is coming. Academia and industry must oversee it — together

Nature. 2024 Dec;636(8042):273. 

doi: 10.1038/d41586-024-03911-3. 

PMID: 39643627.

For the best and safest results, academics and industry scientists must collaborate to guide the development of more powerful forms of AI, argues a Nature editorial. Much of the work to develop such AI is happening in private companies, which don’t always publish openly. Governments, companies, funders and researchers must identify their complementary strengths so that applications of AI research are robust, its risks are mitigated as much as possible, and tech companies’ claims can be verified independently.  

The AI revolution is running out of data. What can researchers do? 

Jones N.

Nature. 2024 Dec;636(8042):290-292. 

A study published this year projected that by 2028, the size of a typical training-data set will equal all of the text that is publicly available online. Put simply, AI is about to run out of training data. Researchers now face a dilemma: find and use training data from untapped sources, such as instant messages, or change course to focus on smaller, more efficient models.  

Optimality of Gerver’s Sofa

Jineon Baek

December 2, 2024

http://arxiv.org/pdf/2411.19826

Ross: no need to ”Pivot ! Pivot ! Pivot !” any more, math is here to help !