MP
Bidirectional communication between nucleotide and substrate binding sites in a type IV multidrug ABC transporter.
Carrillo VHP, Di Cesare M, Rose-Sperling D, Javed W, Neuweiler H, Marcoux J, Orelle C, Jault JM, Hellmich UA.
Nat Commun. 2025 Nov 11;16(1):9921.
doi: 10.1038/s41467-025-65037-y.
PMID: 41219214.
Study of the bidirectional coupling between NBD and substrate-binding cavity in BmrA.
NMR => Nucleotide binding site and communication hinge are bidirectionally coupled.
Fluo, HDX-MS, and cryo-EM => highlight of the allosteric pathways that synchronize ATP hydrolysis with substrate release and uptake.
Mechanistic framework explaining drug polyspecificity and energy efficiency in Type IV ABC exporters.
Assembly and inhibition of transferable TMexCD1-TOprJ1 efflux pump.
Shi Y, Li M, Cui T, Gan J, Huang H, Su Z, Yang R, Zhang X, Zhang H, Feng Y, Feng Y.
Nat Commun. 2025 Nov 14;16(1):10025.
doi: 10.1038/s41467-025-65038-x.
PMID: 41238543.
TMexCD1-TOprJ1 efflux pump = mobile resistance determinant.
Cryo-EM (=> MexD transporter coupled to a OprJ1 outer membrane channel via a OprD) + characterization of inhibitors.
Cryo-EM Structure of the ATP11C Q79E Mutant Reveals the Structural Basis for Altered Phospholipid Recognition.
Qian Y, Gopalasingam CC, Gerle C, Shigematsu H, Abe K, Oshima A.
J Biol Chem. 2025 Nov 12:110935.
doi: 10.1016/j.jbc.2025.110935. Online ahead of print.
PMID: 41237907.
ATP11C (P4-ATPase flippase): structure of the Q79E mutant => single mutation alters phospholipid headgroup recognition.
Cryo-EM => reshaped substrate-binding pocket.
Functional assays => reduced flippase activity and impaired lipid asymmetry maintenance.
A node-localized efflux transporter for loading iron to developing tissues in rice.
Che J, Huang S, Qu Y, Yoshioka Y, Tomita C, Miyaji T, Liu Z, Shen R, Yamaji N, Ma JF.
Nat Commun. 2025 Nov 11;16(1):9916.
doi: 10.1038/s41467-025-64863-4.
PMID: 41219187.
A node-localized iron efflux transporter in rice => loading of iron through a targeted, directional export mechanism.
Localization studies => enrichment at specific vascular junctions controlling nutrient flow.
Mechanistic insights into Enterocin C targeting the undecaprenyl phosphate recycling protein BacA.
Folcher V, Auger R, Louche C, Serror P, Touzé T.
J Biol Chem. 2025 Nov 11:110929.
doi: 10.1016/j.jbc.2025.110929. Online ahead of print.
PMID: 41232670.
Enterocin C is shown to target BacA, a key enzyme, essential for cell wall biosynthesis. Biochemical and structural approaches => Enterocin C binds BacA and blocks its dephosphorylation cycle.
Inhibition => accumulation of cell-wall intermediates and bacterial growth arrest.
Effects of low salinity stress on the taurine metabolism and transport in the Iwagaki oyster Crassostrea nippona.
Gong J, Li Q.
Comp Biochem Physiol Part D Genomics Proteomics. 2025 Dec;56:101593.
doi: 10.1016/j.cbd.2025.101593. Epub 2025 Jul 29.
PMID: 40749601.
Low-salinity stress in the Iwagaki oyster alters taurine metabolism and transporter expression.
Transcriptomic and biochemical analyses => upregulation of taurine synthesis pathways and membrane transporters to maintain osmotic homeostasis.
Taurine levels rise significantly in tissues exposed to hypo-osmotic conditions.
Dissociation kinetics of G proteins from G protein-coupled receptors and effects of allosteric modulation.
Wang J, Nguyen ATN, Adediwura VA, Lu CS, McNeill SM, Jörg M, Scammells PJ, Christopoulos A, May LT, Miao Y.
Proc Natl Acad Sci U S A. 2025 Nov 18;122(46):e2512423122.
doi: 10.1073/pnas.2512423122. Epub 2025 Nov 13.
PMID: 41231956.
Dissociation kinetics of G proteins from GPCRs quantified with single-molecule and computational approaches.
=> allosteric modulators can dramatically alter the lifetime of the GPCR–G protein complex (fast or slow dissociation correlates with distinct signaling outcomes).
Discovering next-generation dopamine transporter drugs with lower abuse potential.
Luo D, Liu Z, Xue W.
Trends Pharmacol Sci. 2025 Nov;46(11):1052-1055.
doi: 10.1016/j.tips.2025.10.002. Epub 2025 Oct 28.
PMID: 41162276.
Strategies to design dopamine transporter (DAT) inhibitors with lower abuse potential.
Highlight of scaffolds that minimize euphoric dopaminergic spikes while retaining clinical efficacy.
Structural insights into an inward proton pumping rhodopsin.
Besaw JE, Peng S, Kuo A, Reichenwallner J, Miller RJD, Brown LS, Ernst OP.
Biophys J. 2025 Nov 11:S0006-3495(25)00746-5.
doi: 10.1016/j.bpj.2025.11.011. Online ahead of print.
PMID: 41229115.
Structure of inward proton-pumping microbial rhodopsin.
Retinal pocket enables reverse-direction proton transport.
Spectroscopic + cryo-EM data => unique arrangement of proton donor/acceptor residues.
Structural basis for Porcupine inhibition.
Black KA, Mobbs JI, Venugopal H, Dite TA, Leis A, Wong LL, Dagley LF, Thal DM, Glukhova A.
Commun Chem. 2025 Nov 12;8(1):348.
doi: 10.1038/s42004-025-01726-5.
PMID: 41225132.
Structure of Porcupine (= acyltransferase essential for Wnt secretion) in complex with inhibitors.
Identification of binding modes that stabilize an inactive conformation.
Continuous exchange of an inner-membrane ring component is required for assembly and function of the type III secretion system.
Brianceau C, Wimmi S, Kronenberger T, Diepold A.
Nat Commun. 2025 Nov 10;16(1):9889.
doi: 10.1038/s41467-025-65973-9.
PMID: 41213942.
Type III secretion system that requires continuous turnover of a key IM ring subunit for proper assembly and function.
Fluo labeling => dynamic exchange of the component even in fully assembled injectisomes.
Structural plasticity is necessary for maintaining a functional T3SS platform.
Dynamic structures of a membrane transporter in native cellular membranes.
Xie H, Gan Y, Zhao W, Duan M, Shen Y, Tan H, Zhang Y, Tong Q, Zhao Y, Yang J.
Sci Adv. 2025 Nov 14;11(46):eadv4583.
doi: 10.1126/sciadv.adv4583. Epub 2025 Nov 12.
PMID: 41223279.
Membrane transporter imaged in its native membrane environment => state-dependent conformational ensembles.
Cryo-ET + subtomogram averaging => shifts between IF- and OF states in situ.
Transitions correlate with local lipid composition and protein crowding.
Molecules
Hybrid Detergents Facilitate Scalable Charge Reduction and Stabilize Membrane Proteins While Retaining Lipid Interactions.
Urner LH, Shutin D, Agasid MT, Robinson CV.
Chemistry. 2025 Nov 12:e03191.
doi: 10.1002/chem.202503191. Online ahead of print.
PMID: 41229277.
Hybrid detergents to improve MP MS by reducing charge states while preserving native lipid contacts.
These amphiphiles combine detergent and polymer features to stabilize complexes => enable hi-res MS of fragile assemblies at scale.
Small Molecules Targeting the Transmembrane Domain.
Wang Y, Wang X.
J Med Chem. 2025 Nov 11.
doi: 10.1021/acs.jmedchem.5c01876. Online ahead of print.
PMID: 41217080.
Small molecules designed to target TM domains.
Advances in hydrophobic ligand design => selective modulation of receptors, channels, and transporters.
=> new therapeutic strategies for traditionally “undruggable” membrane proteins.
Random Heteropolymers Enable Nonspecific Protein Binding and Loop-Mediated Stabilization.
Jin T, Dagadu A, Coley CW, Alexander-Katz A.
ACS Nano. 2025 Nov 10.
doi: 10.1021/acsnano.5c12927. Online ahead of print.
PMID: 41208466.
Random heteropolymers (RHPs) bind proteins nonspecifically and stabilize them via loop-like conformations.
Molecular simulations: RHPs wrap around protein surfaces without requiring sequence recognition.
Membrane-mimetic thermal proteome profiling (MM-TPP) toward mapping membrane protein-ligand dynamic interactions.
Jandu RS, Bhattacharya A, Antony F, Al-Seragi M, Aoki H, Babu M, Duong van Hoa F.
Elife. 2025 Nov 12;14:RP104549.
doi: 10.7554/eLife.104549.
PMID: 41223077.
MM-TPP = thermal proteome profiling method adapted to membrane mimetic environments.
=> quantifies ligand-induced thermal shifts of MPs using detergent or ND based systems.
Methods
MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.
Eluru G, De Gieter S, Schenck S, Stroobants A, Shrestha B, Erbel P, Brunner JD, Efremov RG.
Nat Methods. 2025 Nov 13.
doi: 10.1038/s41592-025-02894-x. Online ahead of print.
PMID: 41233542.
MISO = microfluidic device enabling isolation of protein from a single microbial colony for cryo-EM !
Workflow integrates purification, concentration, and grid preparation in a compact chip.
=> High-resolution structures without large-scale culture.
Membrane and vesicle structure detection in cryo-electron tomography based on deep learning.
Morales-Martínez A, Garduño E, Carazo JM, Sorzano COS, Vilas JL.
J Struct Biol. 2025 Oct 30;217(4):108258.
doi: 10.1016/j.jsb.2025.108258. Epub ahead of print.
PMID: 41176036.
Deep-learning approach developed to detect membranes and vesicle structures in cryo-ET.
=> improves segmentation accuracy in noisy tomograms and enables automated identification of membrane-bound compartments.
Strategies for studying discrete heterogeneity in situ using cryo-electron tomography.
Bartesaghi A.
Curr Opin Struct Biol. 2025 Nov 12;95:103186.
doi: 10.1016/j.sbi.2025.103186. Online ahead of print.
PMID: 41232167.
Strategies to study discrete structural heterogeneity in situ using cryo-ET.
=> computational classification, conformational mapping, and multi-state averaging.
Catch & Release-rapid cost-effective protein purification from plants using a DIY GFP-Trap-protease approach.
Schwartz S, Engstler C, Mühlbauer S, Windenbach E, Wunder T, Kunz HH, Brandt B.
Plant J. 2025 Nov;124(3):e70544.
doi: 10.1111/tpj.70544.
PMID: 41222448.
“Catch & Release” method = DIY protocol to purify plant proteins rapidly using a GFP-Trap and protease-cleavage system.
=> reduces cost, avoids chromatography and yields proteins suitable for biochemical assays.
Microbio
Overexpression of AdeIJK RND efflux pump in Acinetobacter baumannii using the mini-Tn7T-based single copy induction system can lead to lacIq mutation.
Wimalasekara RL, Patidar R, White D, Kumar A.
Microbiol Spectr. 2025 Nov 10:e0160925.
doi: 10.1128/spectrum.01609-25. Online ahead of print.
PMID: 41211987.
Overexpressing the AdeIJK efflux pump in A. baumannii via a mini-Tn7T system unexpectedly induces mutations in lacIq.
=> reduce repression and alter expression levels of the induction system.
=> genetic manipulations of efflux systems may introduce unintended regulatory disruptions !
Heterologous Membrane Proteins Co-Trigger E. coli Filamentation, Polyploidy, and Membrane Remodeling to Boost Bio-Production.
Cen YK, Li JT, Zhou RC, Liu MP, Lu TX, Xiang C, Xue YP, Zheng YG.
Biotechnol Bioeng. 2025 Nov 11.
doi: 10.1002/bit.70107. Online ahead of print.
PMID: 41220207.
Expression of heterologous MPs in E. coli triggers filamentation, polyploidy, and membrane remodeling.
=> enhance biosynthetic capacity for target compounds.
=> stress responses that can be leveraged for improved bioproduction.
Miscellaneous
‘Godfather of AI’ becomes first person to hit one million citations.
Castelvecchi D.
Nature. 2025 Nov 12.
doi: 10.1038/d41586-025-03681-6. Epub ahead of print.
PMID: 41224925.
News feature celebrating the “Godfather of AI” as the first individual to reach one million citations. It reflects on his influential discoveries in deep learning and discusses the broader societal impact of modern AI.
First new type of malaria treatment in decades shows promise against drug resistance.
Lenharo M.
Nature. 2025 Nov 12.
doi: 10.1038/d41586-025-03690-5. Epub ahead of print.
PMID: 41224933.
A novel antimalarial treatment class shows strong efficacy against drug-resistant strains.
Early clinical and parasitological data suggest a new mechanism distinct from current frontline drugs. The therapy could overcome rising global resistance trends. This breakthrough offers long-awaited diversification of the antimalarial pipeline.
Sur quoi tu planches ?
Camille Van Belle
Eleven research teams from Lorraine have transformed years of laboratory work into an accessible comic book to share science with a wider audience. Supported by the ANR and driven by the collective ”Unys”, the project shows how research can help companies, communities, and citizens tackle major societal challenges.
In french only !