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20251029_membrane digest_Methods and Microbio

Methods

Capturing the native structure of membrane proteins using vesicles.

Liu H, Tse CM, Dang S.

Proc Natl Acad Sci U S A. 2025 Sep 9;122(36):e2423407122. 

doi: 10.1073/pnas.2423407122. Epub 2025 Sep 3.

PMID: 40901875.

Method to trap MPs inside native-like vesicles for structural studies. Applications to various transporters demonstrate improved stability and resolution.

 

A Structurally Robust Phospholipid Microtube Constructed by Membrane Phase Separation as a Scaffold for On-Tube Characterization of Membrane-Bound Proteins.

Uchida N, Ishizaka R, Kawakita A, Ueno H, Noji H, Kasai RS, Yokoyama T, Kurihara S, Noguchi T, Watanabe G, Iwasaki A, Ajioka I, Muranishi K, Yoshizawa K, Kanemura S, Okumura M, Muraoka T.

J Am Chem Soc. 2025 Oct 23. 

doi: 10.1021/jacs.5c13384. Online ahead of print.

PMID: 41128357.

Phospholipid microtubes via phase separation as scaffolds for protein characterization. 

Membrane-bound proteins can be reconstituted on-tube for optical and mechanical assays. 

The constructs resist deformation and enable controlled ligand delivery.

 

Advances of 3D microcrystals electron diffraction for transmembrane protein structure determination.

Fiorini G, Schertler GFX, Panneels V.

Biophys J. 2025 Oct 23:S0006-3495(25)00698-8. 

doi: 10.1016/j.bpj.2025.10.027. Online ahead of print.

PMID: 41137388. 

Advances in 3D microcrystal electron diffraction for MP structures. 

It highlights sample preparation, data collection, and phasing strategies. 

Case studies => atomic-level insights from tiny crystals.

 

Hurdles and advancements in experimental membrane protein structural biology.

Bajaj R.

J Struct Biol. 2025 Sep 28:108251. 

doi: 10.1016/j.jsb.2025.108251. Online ahead of print.

PMID: 41027549.

Hurdles and recent progress in experimental MP structural biology. 

Discussion on improving expression and stabilization, and decrease of sample heterogeneity. 

Emerging solutions = novel scaffolds, adaptive detergents, and in situ methods. 

 

Incorporation of transmembrane protein antigens into phospholipid bilayers supported on silica microbeads using membrane fusion with budded virions of recombinant baculovirus.

Nakanishi K, Nishio S, Isozaki Y, Tomita M, Tsumoto K.

Biotechnol Lett. 2025 Sep 25;47(5):115. 

doi: 10.1007/s10529-025-03654-9.

PMID: 40999245.

Method incorporates transmembrane antigens into supported lipid bilayers on silica microbeads using membrane fusion with baculovirus budded virions. 

=> preserves native orientation and post-translational modifications. 

=> Enable high-throughput binding assays and facilitates antigen display for screening and diagnostics.

 

Functional targeting of membrane transporters and enzymes to peroxisomes.

Siu KH, Lee V, Dueber JE.

Nat Chem Biol. 2025 Oct;21(10):1544-1553. 

doi: 10.1038/s41589-025-01948-7. Epub 2025 Jun 16.

PMID: 40524007.

Peroxisomal targeting of MP transporters and enzymes. 

Compartmentalization enables selective metabolite processing and reduces cellular burden. 

PoC pathways demonstrate enhanced flux and minimized cross-talk.

 

MEMO-Stab2: Multi-View Sequence-Based Deep Learning Framework for Predicting Mutation-Induced Stability Changes in Transmembrane Proteins.

Bao Y, Liu Z, Jin H, Wang H, Wang W, Lin GN.

J Chem Inf Model. 2025 Oct 13;65(19):10772-10782. 

doi: 10.1021/acs.jcim.5c01774. Epub 2025 Sep 29.

PMID: 41021316.

MEMO-Stab2 = deep-learning framework that predicts mutation-induced stability changes in MPs from sequence alone. 

Multi-view representations improve generalization across folds. 

 

Machine learning and molecular modeling based design of nanobodies targeting human serotonin transporter and receptor.

Xu B, Liu J, Xue W.

Adv Protein Chem Struct Biol. 2025;147:535-558. 

doi: 10.1016/bs.apcsb.2024.12.004. Epub 2024 Dec 22.

PMID: 40973412.

Machine learning + molecular modeling combined to design nanobodies against the human serotonin transporter and receptor. 

In silico pipelines screen epitopes and affinity, guiding construct selection. 

Biophysical validation confirms binding and modulation. 

 

MPBuild: An Automated Pipeline for High-Fidelity Membrane Protein Simulation System Construction.

Liu Q, Ding W, Yao X, Ling S, Tian C.

J Chem Theory Comput. 2025 Oct 23. 

doi: 10.1021/acs.jctc.5c01078. Online ahead of print.

PMID: 41129804.

MPBuild = automated pipeline to construct high-fidelity simulation systems for MPs. 

It assembles protein, lipids, solvent, and ions with realistic composition and geometry. 

Improved stability and reproducibility across force fields. 

 

Memorization bias impacts modeling of alternative conformational states of solute carrier membrane proteins with methods from deep learning.

Swapna GVT, Dube N, Roth MJ, Montelione GT.

PLoS Comput Biol. 2025 Oct 17;21(10):e1013590. 

doi: 10.1371/journal.pcbi.1013590. eCollection 2025 Oct.

PMID: 41105726. 

Memorization bias in DL models hampers modeling of alternative conformations of solute carrier proteins. Authors show that overfitting to training exemples reduces conformational diversity. 

=> data splitting and ”augmentation strategies” to mitigate bias. 

 

Microbio

AI has designed thousands of potential antibiotics. Will any work?

Fieldhouse R.

Nature. 2025 Oct 3. 

doi: 10.1038/d41586-025-03201-6. Epub ahead of print. 

PMID: 41044271.

Survey on AI-driven discovery of antibiotics amid rising resistance. 

Highlights promising leads but also challenges (e.g synthesis, stability, and scalability). 

 

Porin-Independent Uptake of Small Molecule Antibiotics Facilitated by Escherichia coli Outer Membrane Vesicles.

Wu M, Harrower RM, Li Z, Brown AC.

Biotechnol Bioeng. 2025 Oct 3. 

doi: 10.1002/bit.70078. Online ahead of print.

PMID: 41042070.

E. coli OMVs facilitate porin-independent uptake of small-molecule antibiotics (they act as shuttles that fuse or deliver cargo across the barrier). 

Biochemical => enhanced intracellular accumulation and activity. 

This mechanism reframes OM permeability and drug delivery strategies.

 

Expression of multidrug efflux pump gene acrAB in Escherichia coli: a systematic review and meta analysis.

Bahaj SS, Al-Dhubaibi MS, Noman A, Ali SS, Mehmood H, Alkassar WY, Al-Dhubaibi AM, Mohammed GF, Abd Elneam AI.

BMC Infect Dis. 2025 Oct 21;25(1):1362. 

doi: 10.1186/s12879-025-11778-6.

PMID: 41120967. 

Systematic review and meta-analysis => data on acrAB expression in E. coli. 

Analyses link overexpression with MDR and clinical isolates. 

Identifies methodological heterogeneity and standardization needs. 

AcrAB = surveillance and therapeutic target.

 

Antibacterial effect and MexA efflux pump Inhibition by green-synthesized copper nanoparticles from Mentha piperita.

Ahmed ME, Jameel SK, Alhammer AH.

Mol Biol Rep. 2025 Sep 17;52(1):913. 

doi: 10.1007/s11033-025-11025-w.

PMID: 40960556.

Green-synthesized copper nanoparticles from Mentha piperita show antibacterial activity and inhibit the MexA efflux component. 

MIC reductions and efflux assays support a dual mechanism of membrane stress and pump interference. Nanoparticle characterization ties morphology to potency.

 

EefR mutations drive sanguinarine resistance by activating cryptic multidrug efflux pumps in AcrB-Null Escherichia coli.

Shen HJ, Wang JF, Xue ZJ, Shi JQ, Chen B, Chen DM, Chen NP, Li YD, Qian CD.

Virulence. 2025 Dec;16(1):2566244. 

doi: 10.1080/21505594.2025.2566244. Epub 2025 Sep 29.

PMID: 41017561.

Mutations in the regulator EefR => sanguinarine resistance in AcrB-null E. coli by activating cryptic efflux pumps. 

Transcriptomics and genetics reveal compensatory pathways that restore extrusion capacity. 

=> regulatory plasticity in efflux networks. 

=> disabling a major pump can unmask latent systems.

 

Evolutionary loss of an antibiotic efflux pump increases Pseudomonas aeruginosa quorum sensing mediated virulence in vivo.

Fernandes SE, Ortega H, Vaillancourt M, Galdino ACM, Stotland A, Mun KS, Aguilar D, Doi Y, Lee JS, Burgener EB, Barrick JE, Schertzer JW, Jorth P.

Nat Commun. 2025 Sep 25;16(1):8397. doi: 10.1038/s41467-025-63284-7.

PMID: 40998772

Experimental evolution => loss of a P. aeruginosa efflux pump increases QS-mediated virulence in vivo. 

Reduced efflux => alteration of intracellular signal levels and regulatory circuits. 

Infection models => higher pathogenicity despite increased antibiotic susceptibility. 

The trade-off highlights complex consequences of targeting efflux.

 

Detection of AcrAB efflux pump mediated ciprofloxacin resistance in Escherichia coli and Klebsiella pneumoniae in Nepal.

Kharel S, Rimal S, Neupane B, Sharma BK, Bashyal NS, Shah Y, Chalise BS, Rawal M, Tun MMN, Dumre SP.

BMC Infect Dis. 2025 Oct 2;25(1):1227. 

doi: 10.1186/s12879-025-11555-5.

PMID: 41039364.

Clinical isolates from Nepal analyzed for AcrAB-mediated ciprofloxacin resistance in E. coli and K. pneumoniae. 

Phenotypic tests and molecular markers correlate pump activity with resistance levels. 

Local stewardship and diagnostic needs. 

 

Global transcriptomics and targeted metabolite analysis reveal the involvement of the AcrAB efflux pump in physiological functions by exporting signaling molecules in Photorhabdus laumondii.

Hadchity L, Lanois-Nouri A, Chouchou A, Roche D, Houard J, Claveyroles N, Dauvé A, Imbert J, Gualtieri M, Givaudan A, Carré-Mlouka A, Abi Khattar Z.

Microbiol Spectr. 2025 Oct 7;13(10):e0110625. 

doi: 10.1128/spectrum.01106-25. Epub 2025 Sep 8.

PMID: 40920493. 

Global transcriptomics and targeted metabolomics in Photorhabdus laumondii => AcrAB exports signaling molecules. 

Disruption of the pump perturbs quorum-related pathways and physiology. 

AcrAB: role beyond drug resistance to cellular communication.

 

 

Miscellaneous

Tipsy bats and perfect pasta: Ig Nobels celebrate ‘improbable’ research. 

Simms C.

Nature. 2025 Sep 18. 

doi: 10.1038/d41586-025-03045-0. Epub ahead of print. 

PMID: 40973750.

You may remember the ‘scientifically optimized’ recipe for cacio e pepe. (=> addition of cornstarch.), spotted in the 20250204_membrane digest … this unforgettable study won the Ig Nobel Prize in Physics: well-deserved !

you’ll find see here the full list of winners: 

https://www.nature.com/articles/d41586-025-03045-0?utm_source=Live+Audience&utm_campaign=3985ceb122-nature-briefing-daily-20250919&utm_medium=email&utm_term=0_-33f35e09ea-50537092

 

Physics: John Clarke, Michel Devoret and John Martinis.

Groundbreaking quantum-tunnelling experiments win physics Nobel. 

Gibney E, Castelvecchi D.

Nature. 2025 Oct;646(8085):523-524. 

doi: 10.1038/d41586-025-03194-2. PMID: 41057703.

The Nobel Prize in Physics honors John Clarke, Michel Devoret, and John Martinis for groundbreaking quantum-tunneling experiments. Their work enabled precise control and measurement at mesoscopic scales. These advances underlie today’s superconducting qubits and quantum technologies. The article reviews the arc from fundamental physics to applications.

 

Chemistry: Susumu Kitagawa, Richard Robson and Omar Yaghi.

Chemistry Nobel for scientists who developed massively porous ‘super sponge’ materials. 

Castelvecchi D, Naddaf M.

Nature. 2025 Oct;646(8085):522-523. 

doi: 10.1038/d41586-025-03195-1. 

PMID: 41062753.

The Chemistry Nobel recognizes pioneers of metal–organic frameworks: Susumu Kitagawa, Richard Robson, and Omar Yaghi. Their discovery of porous crystalline networks created “super sponge” materials. Applications span gas storage, separations, and catalysis. The piece charts the field’s evolution from concept to industry.

 

Physiology or Medicine 2025: Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi.

Medicine Nobel goes to scientists who revealed secrets of immune system ‘regulation’. 

Naddaf M, Gibney E.

Nature. 2025 Oct;646(8085):521-522. 

doi: 10.1038/d41586-025-03193-3. 

PMID: 41053362.

The Medicine Nobel goes to Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi for discoveries in immune regulation. They elucidated the role of regulatory T cells and key molecular pathways. These insights enabled therapies for autoimmunity and transplantation. The article outlines the clinical impact of immune tolerance research.