MP
Structural basis of lipopolysaccharide assembly by the outer membrane translocon holo-complex.
Chen H, Siroy A, Morales V, Gurvič D, Quentin Y, Balor S, Abuta’a YA, Marteau M, Froment C, Caumont-Sarcos A, Marcoux J, Stansfeld PJ, Fronzes R, Ieva R.
Nat Commun. 2025 Nov 24;16(1):10404.
doi: 10.1038/s41467-025-65370-2.
PMID: 41285762.
Structural basis of LPS assembly by the OM translocon holo-complex.
CryoEM => how complex coordinates LPS transport and insertion into the OM and mechanistic insights into how Gram-negative bacteria maintain outer membrane integrity.
Small siphophage binding to an open state of the LptDE outer membrane lipopolysaccharide translocon.
Dunbar E, Clark R, Baslé A, Allyjaun S, Newman H, Hubbard J, Khalid S, van den Berg B.
Proc Natl Acad Sci U S A. 2025 Dec 2;122(48):e2516650122.
doi: 10.1073/pnas.2516650122. Epub 2025 Nov 26.
PMID: 41296721.
How small siphophages bind to the open state of the LptDE translocon.
Structural and functional analyses => phage binding stabilizes an open conformation of LptDE, providing insights into phage-host interactions.
The dynamic lateral gate of the mitochondrial β-barrel biogenesis machinery is blocked by darobactin A.
Diederichs KA, Botos I, Hayashi S, Gutishvili G, Kotov V, Kuo K, Iinishi A, Cooper G, Schwarz B, Celia H, Marlovits TC, Lewis K, Gumbart JC, Mindell JA, Buchanan SK.
Nat Commun. 2025 Nov 20.
doi: 10.1038/s41467-025-66417-0. Online ahead of print.
PMID: 41266328.
How darobactin A (cyclic peptide antibiotic) blocks the dynamic lateral gate of the mitochondrial BAM.
cryo-EM and functional assays => darobactin A binds to the lateral gate, preventing substrate insertion and assembly of β-barrel proteins.
Structures of folding intermediates on BAM show diverse substrates fold by a uniform mechanism.
Thomson BD, Marquez MD, Rawson S, Dos Santos TMA, Harrison SC, Kahne D.
bioRxiv [Preprint]. 2025 Oct 17:2025.10.16.682720.
doi: 10.1101/2025.10.16.682720.
PMID: 41280068.
cryo-EM to capture structures of folding intermediates bound to BAM : diverse substrates fold via a uniform mechanism.
The details and entropy demons in a transmembrane allosteric machine.
Luisi BF.
PLoS Biol. 2025 Nov 26;23(11):e3003485.
doi: 10.1371/journal.pbio.3003485. eCollection 2025 Nov.
PMID: 41296789.
Thermodynamic and entropic principles governing transmembrane allosteric machines, such as transporters and receptors, emphasizing the role of allosteric transitions in their function.
Structural characterization of the YbbAP-TesA ABC transporter identifies it as a lipid hydrolase complex that extracts hydrophobic compounds from the bacterial inner membrane.
McAndrew MBL, Cook J, Gill A, Sahoo K, Thomas C, Stansfeld PJ, Crow A.
PLoS Biol. 2025 Nov 25;23(11):e3003427.
doi: 10.1371/journal.pbio.3003427. eCollection 2025 Nov.
PMID: 41289308.
New type VII in the family !
YbbAP-TesA = ABC transporter in bacteria, lipid hydrolase complex that extracts hydrophobic compounds from the IM.
Structural biology and biochemistry => YbbAP-TesA recognizes and transports lipid substrates.
Distinct structural features of Pseudomonas aeruginosa ATP synthase revealed by cryo-electron microscopy.
Sobti M, Gunn AP, Brown SHJ, Zavan L, Fraunfelter VM, Wolfe AL, McDevitt CA, Steed PR, Stewart AG.
Nat Commun. 2025 Dec 9;17(1):406.
doi: 10.1038/s41467-025-67100-0.
PMID: 41366214.
CryoEM => distinct structural features of the ATP synthase from Pseudomonas aeruginosa.
Unique elements in its rotary mechanism and proton translocation pathway, which differ from other bacterial ATP synthases.
Structural insights into MERS and SARS coronavirus membrane proteins.
Mann MK, Yin Y, Marsili S, Xie J, Doijen J, Miller R, Piassek M, van den Broeck N, Kariuki CK, de Gruyter HLM, Leijs AA, Snijder EJ, van Hemert MJ, Keustermans K, Van Gool M, Yu X, Loock MV, Koul A, Sharma S, Van Damme E, Abeywickrema P.
Commun Biol. 2025 Nov 24;8(1):1651.
doi: 10.1038/s42003-025-09042-3.
PMID: 41286109.
Structural insights into the MPs of MERS and SARS coronaviruses.
Key features critical for viral assembly and host interaction.
Engineering Escherichia coli for polyethylene terephthalate powder biodegradation via recoding of an outer membrane protein.
Giménez-Dejoz J, Vidal P, Romero S, Almendral D, Luengo M, Martinez-Sugrañes M, Gonzalez-Alfonso JL, Robles-Martín A, Plou FJ, Bargiela R, Floor M, Ferrer M, Guallar V, Fernandez-Lopez L.
iScience. 2026 Jan 2;29(2):114621.
doi: 10.1016/j.isci.2025.114621. eCollection 2026 Feb 20.
PMID: 41630917.
Functional engineering approach to enhance E. coli’s ability to biodegrade PET powder : potential of synthetic biology for plastic biodegradation and recycling.
Recoding of OmpA to improve PETase enzyme display on the cell surface => significant increase of PET hydrolysis efficiency.
Structure and mechanism of plant urea transporter DUR3.
Wang Y, Green MN, Lin H, Sander AM, Mazurek C, Lin X, Li T, Wang R, Li W, Davis GV, Zhao X, Zhu L, Feng P, Frommer WB, Zhang J, Wudick MM, Fan M.
New Phytol. 2025 Nov 19.
doi: 10.1111/nph.70752. Online ahead of print.
PMID: 41261797.
Structural and functional analysis of the plant urea transporter DUR3 : critical role in nitrogen uptake and recycling.
Cryo-EM and functional assays => conformational changes in TM helices and identification of key residues mediating urea binding and translocation.
Transmembrane proteins in cancer: insights from mechanism to clinical impact.
Shu CW, Chang CH, Wang HH, Liu PF, Chang YF.
Open Biol. 2026 Feb 4;16(2):250259.
doi: 10.1098/rsob.250259.
PMID: 41636247.
Comprehensive overview of the roles and mechanisms of MPs in cancer, from molecular insights to clinical applications.
=> how they contribute to tumor progression, metastasis, and drug resistance => potential as therapeutic targets and biomarkers (including antibody-based therapies and small-molecule inhibitors).
Membranes
The Evolution of Lipids from Solvents to Substrates.
Dutta A, Hannis C, Feinberg N, Columbus L.
Annu Rev Biophys. 2025 Nov 21.
doi: 10.1146/annurev-biophys-021424-012603. Online ahead of print.
PMID: 41270295.
How lipids have evolved from simple solvents to complex substrates that regulate cellular processes : role of lipids in membrane organization, signaling, and energy storage …
Structural Basis of the Membrane Association by the Conserved RocS Membrane-Targeting Sequence in Streptococcus.
Álvarez-Mena A, Morvan E, Lambert C, Kallisseri Parambil A, Lefeuvre M, Xu Z, El Mammeri N, Malard F, Dufourc EJ, Feuillie C, Grangeasse C, Habenstein B.
Adv Sci (Weinh). 2026 Jan 15:e21132.
doi: 10.1002/advs.202521132. Epub ahead of print.
PMID: 41540555.
Structural basis of membrane association by the conserved RocS membrane-targeting sequence in Streptococcus.
Structural biology and biophysical assays => how RocS interacts with the membrane, facilitating its localization and function.
Systematic analyses of lipid mobilization by human lipid transfer proteins.
Titeca K, Chiapparino A, Hennrich ML, Türei D, Moqadam M, Talandashti R, Cuveillier C, van Ek L, Zukowska J, Triana S, Echelard F, Nielsen IØ, Foged MM, Gehin C, Olechnovic K, Grudinin S, Saez-Rodriguez J, Alexandrov T, Maeda K, Reuter N, Gavin AC.
Nature. 2026 Jan 7.
doi: 10.1038/s41586-025-10040-y. Epub ahead of print.
PMID: 41501472.
Systematic analysis of lipid mobilization by human lipid transfer proteins.
Advanced mass spectrometry and computational modeling => mapping of the interactions between lipid transfer proteins and their lipid substrates.
Reveals how these proteins regulate lipid distribution and homeostasis in cells.
Tubulation of membrane sheets by curvature-inducing proteins.
Ghazizadeh E, Zeidi M, Stroberg W.
Biochim Biophys Acta Biomembr. 2025 Nov 18:184484.
doi: 10.1016/j.bbamem.2025.184484. Online ahead of print.
PMID: 41265671.
How curvature-inducing proteins tubulate membrane sheets (critical for cellular organization and trafficking).
Biophysical experiments and theoretical modeling => how these proteins deform membranes to create tubular structures and mechanical principles underlying membrane remodeling.
Protein drift-diffusion in membranes with non-equilibrium fluctuations arising from gradients in concentration or temperature.
Jasuja D, Atzberger PJ.
PLoS Comput Biol. 2025 Nov 21;21(11):e1013678.
doi: 10.1371/journal.pcbi.1013678. eCollection 2025 Nov.
PMID: 41270151.
Protein drift-diffusion in membranes under non-equilibrium conditions (such as concentration or temperature gradients).
Computational models to simulate how proteins move and interact within membranes, revealing the impact of environmental fluctuations on their dynamics.
Triangulating a Tightly Bound Lipid on a Membrane Protein by Paramagnetic Solid-State NMR.
Vaz RF, Brown LS, Ladizhansky V.
J Am Chem Soc. 2026 Feb 5.
doi: 10.1021/jacs.5c22235. Online ahead of print.
PMID: 41641854.
Method for triangulating tightly bound lipids MPs using paramagnetic ssNMR. => precise mapping of lipid-protein interactions, revealing how specific lipids stabilize and modulate protein function.
Molecules
Overcoming divalent cation sensitivity is not the only challenge for functional study of ABC transporters within polymer lipid particles.
Hawkins OP, Potter TJ, Broadbent LM, Kitchen P, Goddard AD, Rothnie AJ.
Biosci Rep. 2026 Feb 4;46(2):BSR20250256.
doi: 10.1042/BSR20250256.
PMID: 41636053.
Challenges of studying ABC transporters within polymer lipid particles, focusing on overcoming divalent cation sensitivity.
=> Alternative strategies (AASTY polymers) to maintain transporter functionality in artificial membrane environments.
Methods
A miniaturized, high-throughput aqueous solvent-centric method for protein solubility screening.
Adrian Svoboda, Marina Molineris, Theodora Tureckiova, Klara Hlouchova, Tomas Pluskal, and Teo Hebra
bioRxiv posted 14 January 2026.
doi:10.1101/2025.06.16.659941.
Miniaturized HT method for screening protein solubility in aqueous solvents, facilitating large-scale studies. Useful for optimizing conditions for MP purification and crystallization.
In Situ Structure Determination of a Membrane Protein in Native Cellular Membranes by Proton-Detected Solid-State NMR.
Xie H, Zhao W, Xiao H, Zhang Y, Shen Y, Gan Y, Tong Q, Zhao Y, Tan H, Yang J.
bioRxiv [Preprint]. 2025 Oct 29:2025.10.28.685061.
doi: 10.1101/2025.10.28.685061.
PMID: 41278784.
Proton-detected ssNMR for determining the structure of MPs directly within native cellular membranes, without the need for protein purification or reconstitution.
Expression, purification, and reconstitution of small-conductance mechanosensitive channel into lipid bilayer: ready for solid-state NMR study.
Meng S, Gao Z, Lin Y, Zhang Y, Xie H, Yang J, Tong Q.
Protein Expr Purif. 2026 Feb 1:106897.
doi: 10.1016/j.pep.2026.106897. Online ahead of print.
PMID: 41633421.
Protocol for the expression, purification, and reconstitution of a MscS into lipid bilayers.
2D 15N-13Cα spectroscopy of theMscS proteoliposomes => well-resolved spectra by ssNMR.
Mass spectrometry-based strategies for membrane protein pharmacology.
Reiter AH, Fehr A, Florea R, Floyd BM, Schuster D.
Trends Pharmacol Sci. 2025 Nov 20:S0165-6147(25)00236-6.
doi: 10.1016/j.tips.2025.10.012. Online ahead of print.
PMID: 41271450.
Mass spectrometry-based strategies for studying MP pharmacology : identification of drug-binding sites, characterization of protein-lipid interactions, and elucidation MoA.
Multiple protein structure alignment at scale with FoldMason.
Gilchrist CLM, Mirdita M, Steinegger M.
Science. 2026 Jan 29;391(6784):485-488.
doi: 10.1126/science.ads6733. Epub 2026 Jan 29.
PMID: 41610233.
FoldMason = tool for large-scale multiple protein structure alignment.
Useful for identifying structural homologies and functional similarities across proteins.
Microbio
Modeling and Functional Characterization of Reconstituted Efflux Pump Components from Heterologous Gram-Negative Bacteria.
Bhowmik P, Shanbhag AP, Venkatesan S, Bharatham N, Datta S, Ramachandran V.
ACS Infect Dis. 2026 Jan 28.
doi: 10.1021/acsinfecdis.5c00612. Epub ahead of print.
PMID: 41603438.
Combination of computational modeling and functional assays to understand how efflux pump components from heterologous Gram-negative bacteria assemble and function across different species.
Characterization of Enterobacter cloacae complex clinical isolates: comparative genomics and the role of the efflux pump AcrAB-TolC over-expression and NDM-1 production.
Jiang N, Pu F, Wang W, Wang D, He J.
Front Cell Infect Microbiol. 2025 Nov 7;15:1705370.
doi: 10.3389/fcimb.2025.1705370. eCollection 2025.
PMID: 41278467.
Characterization of clinical isolates of the Enterobacter cloacae complex, focusing on the role of AcrAB-TolC EP overexpression and NDM-1 production in AtbR.
Comparative genomics to identify genetic factors contributing to resistance.
Highlights the importance of efflux pumps and β-lactamases in MDR.
Advancing equity in antimicrobial resistance research and policy.
Dobreva Z, Centner CM, Bertagnolio S.
Trends Microbiol. 2025 Nov 17:S0966-842X(25)00334-8.
doi: 10.1016/j.tim.2025.11.007. Online ahead of print.
PMID: 41253615.
This article discusses the importance of advancing equity in AMR research and policy : disparities in access to resources, data, and treatments, and propose strategies to promote inclusivity and collaboration.
Miscellaneous
Low-cost highlighter nanoparticles for highly efficient multistep excitation energy transfer.
Piard J, Degano I, Doré C, Audibert JF, Grazon C, Allain C, Bertrand L.
Spectrochim Acta A Mol Biomol Spectrosc. 2026 Jan 24;352:127477.
doi: 10.1016/j.saa.2026.127477. Epub ahead of print.
PMID: 41638044.
Low-cost highlighter nanoparticles designed for highly efficient multistep excitation energy transfer.
=> how nanoparticles can be engineered to optimize energy transfer processes, making them ideal for applications in bioimaging, sensing, and optoelectronics.
NPs unique optical properties enable precise control over energy transfer pathways, enhancing their performance in complex environments.
‘Remote controlled’ proteins illuminate living cells.
Callaway E.
Nature. 2026 Jan 21.
doi: 10.1038/d41586-026-00204-9. Epub ahead of print.
PMID: 41565965.
Engineering of magnetically controlled fluorescent proteins that can be remotely dimmed and brightened in bacterial cells and in animals.
=> Manipulation of the brightness of the protein in E. coli with a combination of magnets and radio waves.
=> towards the development of remote-controlled biosensors, or even therapies that can be turned on and off when needed ?
Does AI already have human-level intelligence? The evidence is clear.
Chen EK, Belkin M, Bergen L, Danks D.
Nature. 2026 Feb;650(8100):36-40.
doi: 10.1038/d41586-026-00285-6.
PMID: 41629664.
Has AI achieved human-level intelligence ?
Evidence from cognitive science, computational benchmarks, and real-world applications.
AI still lack the general adaptability, creativity, and contextual understanding characteristic of human intelligence.
=> importance of distinguishing between narrow AI capabilities and broader, human-like cognition.
The Guthman Musical Instrument Competition is back !
I am sure you all remember last year’s 3 Axis MIDI Guitar, Hacked Double Trumpet (🇫🇷🐓) and Mulatar (see 20250303_membrane digest and https://www.popsci.com/technology/2025-guthman-musical-instrument-competition-finalists/).
2026 edition is on and the winner will be decided at the end of a weekend-long showcase of all 10 finalists in March.
Here are the finalists :
https://www.popsci.com/technology/guthman-musical-instrument-finalists/