MP

Unveiling conformation-selective regulation of the norepinephrine transporter.

Zhang H, Zhang T, Wang D, Dai A, Mao J, Chen Q, Du T, Lu X, Hao Y, Zhang C, Yin YL, Hu W, Pan B, Jin S, Jiang M, Si Y, Yuan Q, Wang MW, Zheng M, Wang Z, Yang D, Xu HE, Jiang Y.

Cell. 2025 Nov 26;188(24):6861-6872.e14. 

doi: 10.1016/j.cell.2025.10.002. Epub 2025 Oct 24.

PMID: 41138730.

Norepinephrine transporter (NET) regulates neurotransmitter homeostasis and is a key target for antidepressants and psychostimulants.

Here : cryo-EM and functional assays => conformation-selective mechanism where specific ligands stabilize NET in either an IF- or OF-state, influencing transport activity.

Molecular Insights into CLD Domain Dynamics and Toxin Recruitment of the HlyA E. coli T1SS.

Gentile R, Schott-Verdugo S, Khosa S, Günes C, Bonus M, Reiners J, Smits SHJ, Schmitt L, Gohlke H.

J Mol Biol. 2025 Dec 15;437(24):169485. 

doi: 10.1016/j.jmb.2025.169485. Epub 2025 Oct 11.

PMID: 41083144.

T1SS in E. coli exports toxins like HlyA, but the molecular mechanisms underlying toxin recruitment and secretion remain unclear. 

Here : cryo-EM, MD, and biochemical assays to elucidate the dynamics of the calcium-binding domain (CLD), critical for toxin recognition by the T1SS. 

=> CLD conformational changes facilitate toxin docking and translocation : role of calcium in stabilizing these interactions. 

Functional diversity and molecular interactions of small membrane proteins in bacteria.

Yuan J, Koch HG, Berghoff BA.

Microlife. 2025 Nov 7;6:uqaf035. 

doi: 10.1093/femsml/uqaf035. eCollection 2025.

PMID: 41312160.

Small membrane proteins (SMPs) in bacteria are often overlooked despite their roles in transport, signaling, and virulence. 

Here : exploration of the functional diversity of SMPs; bioinformatics, structural modeling, and functional assays => classify SMPs and identify conserved motifs linked to specific functions. 

Targeted protein degradation in the transmembrane and extracellular space.

Zhu R, Zhang H, Chen PR.

Science. 2025 Nov 27;390(6776):eadx5094. 

doi: 10.1126/science.adx5094. Epub 2025 Nov 27.

PMID: 41308155.

Targeted protein degradation (TPD) has revolutionized drug discovery, but its application to MPs and extracellular proteins remains challenging. 

Here : novel TPD platform that hijacks endogenous quality control pathways to degrade membrane and secreted proteins. 

=> degradation of disease-relevant targets, including receptors and efflux pumps, using both in vitro and in vivo models. 

=> expands the scope of TPD to previously inaccessible protein classes.

=> new opportunities for therapeutic intervention.

Broad-Spectrum Naphthyl-Substituted Diaminoquinolines Inhibiting the AdeG Efflux Pump of Acinetobacter baumannii.

Tambat R, Sariyer AS, Sariyer E, Olvera M, Farjana M, D’Cunha N, Walker JK, Zgurskaya HI.

ACS Infect Dis. 2026 Feb 13;12(2):588-599. 

doi: 10.1021/acsinfecdis.5c00722. Epub 2026 Jan 5.

PMID: 41490277.

AdeG in A. baumannii = major contributor to MDR, limiting treatment options for infections. 

Here : identification of naphthyl-substituted diaminoquinolines as potent inhibitors of AdeG.

Microbiological assays + MD + resistance profiling => mechanism of inhibition and the broad-spectrum activity of these compounds.

Substrate Specificity Checkpoints of the Multidrug Efflux Pump MexF from Pseudomonas aeruginosa.

Uddin MR, Gervasoni S, Malloci G, Ruggerone P, Zgurskaya HI.

ACS Infect Dis. 2026 Feb 13;12(2):611-622. 

doi: 10.1021/acsinfecdis.5c00760. Epub 2026 Jan 16.

PMID: 41543281.

Molecular basis of MexF (P. aeruginosa) substrate specificity. 

Computational modeling and functional assays => key residues and conformational states that govern substrate recognition and transport. 

Multi-checkpoint mechanism where MexF selectively binds and extrudes substrates based on their physicochemical properties. 

Do RND efflux pumps require protomeric cooperativity within the trimer to mediate antimicrobial resistance? 

Zhang Z, Klenotic PA, Hung W-T, Maharjan R, Kundracik E, Gregor WD, Yu EW.

Microbiol Mol Biol Rev. 2025 Dec 3:e0030425. 

doi: 10.1128/mmbr.00304-25. Epub ahead of print. 

PMID: 41334924.

Role of protomeric cooperativity in the function of RND efflux pumps is debated. 

Review focusing structural, biochemical, and computational evidence to evaluate whether cooperative interactions between protomers are essential for pump activity. 

=> conformational coupling within the trimer may enhance substrate binding, transport, and resistance, while also highlighting gaps in current understanding. 

Molecular mechanism of action of small molecule SMT-738 on bacterial lipoprotein transporter LolCDE.

Li H, Zhu X, Zhang D, Duan X, Li J, Qu Y, Li D, Zhang Z, Dong H, Guo FB, Dong C.

Nat Commun. 2026 Feb 9. 

doi: 10.1038/s41467-026-69411-2. Online ahead of print.

PMID: 41663437.

LolCDE => lipoprotein trafficking in Gram-negative bacteria. 

Here : cryo-EM, biochemical assays, and MD to show how SMT-738 (small molecule that inhibits LolCDE by disrupting its ATP-dependent transport cycle) binds to LolCDE, locking it in a non-functional conformation. 

Membranes

Regulation of membrane protein activity by cyclopropane fatty acids in Escherichia coli lipid environment.

Hori K, Hamamoto S, Shinoda K, Nakamura K, Iwama R, Ujihara T, Kosono S, Nishiyama M, Kawasaki H, Tomita T.

Commun Biol. 2025 Nov 27. 

doi: 10.1038/s42003-025-09234-x. Online ahead of print.

PMID: 41310198.

Cyclopropane fatty acids (CFAs) = components of bacterial membranes that modulate membrane fluidity and protein function. 

Here : how CFAs in E. coli regulate the activity of MPs by altering lipid packing and bilayer properties (combination of biophysical assays and MD simulations).

Polymyxins slow down lateral diffusion of proteins and lipopolysaccharide in the E. coli outer membrane.

Prakaash D, Khalid S.

Commun Biol. 2025 Dec 5;8(1):1751. 

doi: 10.1038/s42003-025-09161-x.

PMID: 41350394.

Single-molecule tracking and MD to show that polymyxins slow the lateral diffusion of proteins and LPS in the E. coli OM. 

The authors propose that this reduction in membrane fluidity compromises barrier function and sensitizes bacteria to other antibiotics.

Planar Lipid Bilayers and Liposomes: Essential Models for Advancing Protein Structure and Function Research. 

Bukiya AN, Rosenhouse-Dantsker A.

Adv Exp Med Biol. 2026;1496:363-395. 

doi: 10.1007/978-3-032-07511-6_14. 

PMID: 41652171.

Reviews how planar lipid bilayers and liposomes enable high-resolution structural analysis, functional assays, and biophysical characterization of MPs, including ion channels, transporters, and receptors. 

=> Advances in bilayer and liposome preparation, such as the incorporation of natural lipid mixtures and asymmetric bilayers, which enhance the physiological relevance of in vitro studies. 

Designing biologically-relevant cell membrane models with natural lipid mixtures.

Batchu KC, Corucci G, Laux V, Gabel F, Fragneto G, Luchini A.

Biochim Biophys Acta Biomembr. 2026 Jan;1868(1):184474. 

doi: 10.1016/j.bbamem.2025.184474. Epub 2025 Oct 13.

PMID: 41093266.

Traditional artificial bilayers often lack the complexity of native membranes. Here : method for designing biologically relevant membrane models using natural lipid mixtures that mimic the composition and asymmetry of cellular membranes. 

The authors demonstrate how these models improve the functional reconstitution of membrane proteins, including transporters and receptors.

Single-Particle Characterization Reveals Heterogeneous Extracellular Vesicle Fusion with Liposomes.

Mizenko RR, Arun V, Meshkanian D, Lowe NM, Mohabbat H, Wang A, Carney RP.

Small Methods. 2026 Feb 6:e01195. 

doi: 10.1002/smtd.202501195. Online ahead of print.

PMID: 41649044.

EVs play key roles in intercellular communication, but their fusion mechanisms with target membranes remain poorly understood. 

Here : single-particle imaging to characterize the heterogeneous fusion of EVs with liposomes, revealing distinct fusion pathways and efficiency factors. 

=> lipid composition and vesicle size influence fusion dynamics, providing insights into EV-mediated cargo delivery. 

Impact of lipid asymmetry on membrane biophysical properties: Insights from molecular dynamics simulations.

Zhang Y, Lou J.

Quant Biol. 2025 Jan 27;13(2):e89. 

doi: 10.1002/qub2.89. eCollection 2025 Jun.

PMID: 41675511/   

MD simulations to explore how lipid asymmetry affects membrane fluidity, curvature, and protein-lipid interactions. 

=> asymmetric lipid distribution alters the lateral pressure profile and modulates the activity of embedded proteins. 

Molecules

Lateral lipid packing governs bilayer solubilization by styrene-maleic acid copolymers: a case study with cardiolipin-containing membranes.

Iovine JC, Garrett BT, Alder NN.

Biochim Biophys Acta Biomembr. 2026 Jan;1868(1):184470. 

doi: 10.1016/j.bbamem.2025.184470. Epub 2025 Oct 5.

PMID: 41057051.    

How lipid packing and CL content influence SMA-mediated bilayer solubilization. 

=> tighter lipid packing reduces SMA insertion and solubilization efficiency, providing guidelines for optimizing SMA-based membrane protein extraction. 

Mechanistic insights of arginine-based surfactant interaction with bacteria and mammalian model lipid membranes.

Sabatie AE, Hermet M, Fait ME, Valdivia Pérez JA, Morcelle S, Fanani ML.

Biochim Biophys Acta Biomembr. 2026 Feb 3:184508. 

doi: 10.1016/j.bbamem.2026.184508. Online ahead of print.

PMID: 41643760.

Arginine-based surfactants = promising antimicrobial agents. 

Here : biophysical assays and MD to compare how these surfactants interact with bacterial and mammalian model membranes. 

=> arginine-based surfactants disrupt bacterial membranes through selective lipid extraction and pore formation, while sparing mammalian membranes.

Methods

Single Molecule Force Spectroscopy to Probe Intermediates and Energetics of Membrane Protein Folding. 

Jacobson DR

Chem Rev. 2026 Feb 6. 

doi: 10.1021/acs.chemrev.5c00612. Epub ahead of print. 

PMID: 41651456.

MP folding is a complex process involving multiple intermediates, but traditional ensemble methods lack the resolution to characterize these states. 

Here : SMFS (single-molecule force spectroscopy) to dissect the folding pathways and energetics of MPs. 

=> transient intermediates, folding forces, and the role of the lipid environment in stabilizing folded states : critical for understanding MP biogenesis and designing folding modulators.

MemConverter: An Iterative Pipeline for Reprogramming Protein Localization in Membrane or Aqueous Solution.

Li J, Guo H, Song C.

J Chem Theory Comput. 2026 Feb 8. 

doi: 10.1021/acs.jctc.5c01859. Online ahead of print.

PMID: 41656617.

Reprogramming protein localization between membrane and aqueous environments is a challenge for synthetic biology and drug design. 

Here : MemConverter = iterative computational pipeline that predicts and optimizes mutations to switch protein localization. 

Validation using experimental assays, showing its efficacy in redesigning membrane proteins for soluble expression and vice versa. 

MemPPI platform for measuring and engineering membrane protein-protein interactions in mammalian cells via split nanoluciferase.

Tang W, Jojoa-Cruz S, Li J, Goldenfeld G, Mravic M.

Protein Sci. 2026 Mar;35(3):e70496. 

doi: 10.1002/pro.70496.

PMID: 41676932.     

MemPPI => platform using split nanoluciferase to quantify PPIs in mammalian cells with high sensitivity and spatial resolution. 

Utility in mapping interactions within efflux pumps and receptor complexes, as well as engineering novel PPIs. 

Advanced Computational Methods in Protein Simulations: A Case Study of Enhanced Sampling Applied to Membrane Transporters.

Colburn JD, Lichtinger SM, Biggin PC.

Adv Exp Med Biol. 2026;1496:77-119. 

doi: 10.1007/978-3-032-07511-6_3.

PMID: 41652160.

Enhanced sampling methods = essential for simulating the complex conformational landscapes of MPs, but often exhibit slow dynamics. 

Here : review on advanced computational techniques, such as metadynamics and Gaussian accelerated MDs, applied to membrane transporters. 

=> case studies illustrating how these methods capture rare events (e.g substrate binding and transport) + best practices for setup and analysis.

Methodological Approaches for Extraction, Chromatographic and Mass Spectrometric Analysis of Lipids.

Cummings BS.

Biomed Chromatogr. 2026 Mar;40(3):e70388. 

doi: 10.1002/bmc.70388.

PMID: 41673723.

Lipid analysis = crucial for understanding membrane composition and function, but methodological challenges persist in extraction, separation, and identification. 

Here : comprehensive guide to modern lipidomic techniques, including optimized extraction protocols, high-resolution chromatography, and MS. 

=> applications in studying MP-lipid interactions and tools for quantitative and spatial lipidomics.

Microbio

Membrane-associated effluxosomes coordinate multi-metal resistance in Mycobacterium tuberculosis. 

Dupuy P, Boudehen YM, Faucher M, Buglino JA, Fay A, Cantaloube S, Grimoire Y, Marcoux J, Levet F, Bettarel L, Voisin B, Rech J, Bouet JY, Saurel O, Sibarita JB, Glickman M, Gutierrez C, Neyrolles O. 

EMBO J (2026). 

https://doi.org/10.1038/s44318-026-00715-1.

Mycobacterium tuberculosis employs specialized membrane-associated effluxosomes to resist multiple metals, contributing to its survival in hostile environments. 

Here : cryoET, proteomics, and functional assays to characterize these effluxosomes, revealing their assembly and substrate specificity. 

=> effluxosomes coordinate the export of toxic metals : mechanistic basis for their role in bacterial persistence. 

Regulatory mechanism of the oprM gene in colistin resistance of acinetobacter baumannii.

Wang L, Wang Y, Xu H, Li W, Ruan J.

J Infect Public Health. 2025 Nov 24;19(2):103068. 

doi: 10.1016/j.jiph.2025.103068. Online ahead of print.

PMID: 41308409.

Colistin resistance in Acinetobacter baumannii = growing clinical concern. 

Here : role of the oprM gene in colistin resistance. 

Identification of transcriptional regulators and environmental cues that modulate oprM expression, linking efflux pump activity to resistance phenotypes.

Deciphering the roles of AcrAB-TolC efflux pump in promoting the transmission of antibiotic resistance.

Zhu S, Yu F, Yang B, Zhang M, Zhang H, Wang Z, Liu Y.

Drug Resist Updat. 2026 Mar;85:101358. 

doi: 10.1016/j.drup.2026.101358. Epub 2026 Jan 19.

PMID: 41570365

Review synthesizing evidence on how AcrAB-TolC facilitates the spread of resistance genes through HGT and persistence under antibiotic pressure. 

The authors discuss the pump’s interaction with mobile genetic elements and its impact on the evolution of multidrug-resistant strains.

Collateral sensitivity and genetic vulnerability of antibiotic resistance.

Yang K, Rasouly A, Nudler E.

Trends Microbiol. 2025 Dec 2:S0966-842X(25)00328-2. 

doi: 10.1016/j.tim.2025.11.002. Online ahead of print.

PMID: 41339140.     

Collateral sensitivity (resistance to one antibiotic increases susceptibility to another) = potential strategy to combat MDR. 

Here : review exploring genetic and mechanistic basis of collateral sensitivity, focusing on how resistance mutations create vulnerabilities in bacterial physiology. 

=> strategies to exploit these vulnerabilities, such as cyclic antibiotic regimens and adjuvant therapies. 

Miscellaneous

Time-of-day immunochemotherapy in non-small cell lung cancer: a randomized phase 3 trial. 

Huang Z, Zeng L, Ruan Z, Zeng Q, Yan H, Jiang W, Xiong Y, Zhou C, Yang H, Liu L, Dai J, Zou N, Xu S, Wang Y, Wang Z, Deng J, Chen X, Wang J, Xiang H, Li X, Duchemann B, Chen G, Xia Y, Mok T, Scheiermann C, Lévi F, Yang N, Zhang Y.

Nat Med. 2026 Feb 2. 

doi: 10.1038/s41591-025-04181-w. Epub ahead of print. 

PMID: 41629425.

Administering immunochemotherapy at specific times of day may improve efficacy and reduce toxicity in non-small cell lung cancer (NSCLC) patients. 

Here : randomized phase 3 trial that compares morning versus evening administration of standard immunochemotherapy regimens.

=> evening treatment significantly improves progression-free survival and overall response rates. 

The study attributes these benefits to circadian rhythms influencing drug metabolism, immune cell activity, and tumor cell susceptibility. 

Coffee linked to slower brain ageing in study of 130,000 people. 

Heidt A.

Nature. 2026 Feb 9. 

doi: 10.1038/d41586-026-00409-y. Epub ahead of print. 

PMID: 41667812.

Regular caffeine intake from coffee and tea might slow cognitive decline and reduce a person’s risk of dementia, a huge study suggests (caffeine-drinking habits of more than 130,000 people over four decades). 

=> drinking 2–3 cups of coffee or 1–2 cups of tea a day = associated with the greatest reductions in rate of cognitive decline, a result that held true even in people with a genetic variant called APOE4, which is associated with Alzheimer’s disease. 

“However, because it uses observational, not experimental, evidence, the findings can only be considered suggestive,” says cardiometabolic medicine specialist Naveed Sattar.

Public-speaking tips from the experts: what scientists can learn from comics, musicians and actors. 

Tregoning J.

Nature. 2026 Feb 10. 

doi: 10.1038/d41586-025-04166-2. Epub ahead of print. 

PMID: 41667814.

Effective public speaking = critical skill for scientists, yet many struggle to engage audiences beyond their technical presentations. 

Here : techniques (storytelling, pacing, and emotional connection) from comedians, musicians, and actors. 

Experts recommend practicing clarity, using analogies, and embracing vulnerability to make complex ideas accessible and memorable.