MP
In situ structure of a gap junction-stomatin complex.
Rosenkranz N, Birtasu AN, Wieland K, Rehm L, Sharma R, Vats A, Manger S, Srivastava A, Bhattacharya A, Hummer G, Frangakis AS, Gottschalk A.
Sci Adv. 2025 Nov 7;11(45):eaea8596.
doi: 10.1126/sciadv.aea8596. Epub 2025 Nov 5.
PMID: 41191766.
Native architecture of a gap-junction/stomatin complex within membranes.
in-situ cryo-techniques => stomatin associates at the periphery of the gap-junction pore, modulating its assembly and intercellular coupling.
Functional assays => disrupting the stomatin–connexin interface impairs gap-junction permeability and intercellular passage of small molecules.
Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with Gs.
Merino F, Köck Z, Ermel U, Dahlhaus P, Grimm A, Seybert A, Kubicek J, Frangakis AS, Dötsch V, Hilger D, Bernhard F.
Structure. 2025 Nov 6;33(11):1867-1877.e5.
doi: 10.1016/j.str.2025.07.020. Epub 2025 Aug 25.
PMID: 40858117.
full-length human β1AR synthetized via a cell-free system + inserted into NDs, + cryo-EM structure in complex with the heterotrimeric Gs protein.
=> previously unresolved ICL3 extends TM5 and makes contacts with Gαs.
Mutagenesis and signaling assays => ICL3 increases cAMP production by promoting more extensive receptor-G protein contact surfaces.
Cysteine-mediated structural stabilization of the tetrameric GlpF.
Siligan C, Gratzl S, Pluhackova K, Goessweiner-Mohr N, Pohl P, Horner A.
Eur Biophys J. 2025 Nov 3.
doi: 10.1007/s00249-025-01803-6. Online ahead of print.
PMID: 41182398.
Cysteine contribute to the structural stability of the tetrameric aquaporin/channels GlpF in lipid membranes.
Formation of specific disulfide or thiol–thiol interactions among cysteines enhances the tetramer lifetime under denaturing conditions.
Biophysical assays => mutating these cysteines reduces tetramer integrity and channel function, linking chemical stabilization to assembly.
Characterization of an Open-Channel Structure and Lateral Conduction Pathway in the Cation-Selective Pentameric Ligand-Gated Ion Channel, ELIC.
Mark J Arcario, Elizabeth J. Wu-Chen, Jérôme Hénin, Grace Brannigan, and Wayland Wing-Lun Cheng.
bioRxiv posted 8 November 2025.
doi:10.1101/2025.11.06.686614.
Structure of the bacterial PLGIC ELIC in an open-channel conformation + lateral conduction pathway beyond the canonical pore.
MD and electrophysiology => ions may escape laterally through side-gates.
The locking mechanism of human TRPV6 inhibition by intracellular magnesium.
Neuberger A, Shalygin A, Veretenenko II, Trofimov YA, Gudermann T, Chubanov V, Efremov RG, Sobolevsky AI.
Nat Commun. 2025 Nov 6;16(1):9826.
doi: 10.1038/s41467-025-65919-1.
PMID: 41198662.
Intracellular Mg²⁺ binds to the TRPV6 channel and locks it in a closed state, thus preventing Ca²⁺ influx.
Structural data => distinct Mg²⁺-binding site that triggers conformational changes stabilizing the non-conductive state.
Functional assays => mutations at the site abolish Mg²⁺ inhibition and lead to dysregulated Ca²⁺ entry.
Asymmetric Dynamics Between the Protomers of the σ2 Receptor Homodimer.
Xu M, Alyemni S, Borin VA, Majumder R, Nucci NV, Keck T, Frankowski K, Agarwal PK, Haider S.
J Chem Inf Model. 2025 Nov 6.
doi: 10.1021/acs.jcim.5c02174. Online ahead of print.
PMID: 41196005.
σ2 receptor homodimer = asymmetric dynamics between its two protomers. MD + experimental validation => distinct conformational states for each protomer under ligand binding, with implications for selectivity.
One protomer = active-like conformation / the other remains in an inactive state => differential regulation.
Deciphering the molecular mechanism of the bacterial division motor TolQRA.
Shen C, Xie T, Luo Y, Zhao F, Wang X, Zhang Z, Pang J, Zhang J, Dong X, Chang S, Ding BS, Ying B, Chi W, Su Z, Zhou R, Tang X, Dong H.
Cell Discov. 2025 Nov 4;11(1):87.
doi: 10.1038/s41421-025-00841-w.
PMID: 41184225.
Molecular mechanism of the bacterial division motor complex TolQRA, which couples pmf to OM constriction.
Structural, biochemical and in vivo analyses => conformational changes in TolQRA transduce energy to drive periplasmic bridging and cell-wall remodeling.
Mechanistic model in which TolA extension pulls the OM inward synchronized with PG synthesis.
Distinctive Properties of Mla Proteins Differentiate Them From Classical ABC Transporter Components.
Dutta A, Patel S, Kanaujia SP.
Proteins. 2025 Oct 5.
doi: 10.1002/prot.70064. Epub ahead of print.
PMID: 41047745.
Proteins from the Mla (maintenance of lipid asymmetry) system diverge fundamentally from canonical ABC transporter architectures in mechanism and structure.
Mla components do not rely on the typical ”ABC” nucleotide-binding and translocation cycle, but instead operate via alternate lipid-transfer pathways.
Unique lipid-binding sites and regulatory features => the Mla system represents a distinct class of membrane lipid-maintenance machinery.
Structural basis of isethionate transport by a TRAP transporter from a sulfate-reducing bacterium.
Newton-Vesty MC, Scalise M, Jamieson SA, Currie MJ, Brown HG, Valimehr S, Tillett ZD, Hall KR, Quan S, Allison JR, Whitten AE, Panjikar S, Indiveri C, Hanssen E, Mace PD, North RA, Dobson RCJ, Davies JS.
Structure. 2025 Nov 5:S0969-2126(25)00398-3.
doi: 10.1016/j.str.2025.10.011. Online ahead of print.
PMID: 41197622.
High-resolution structure of a substrate-binding domain + TM module of a TRAP (tripartite ATP-independent periplasmic) transporter that imports isethionate in a sulfate-reducing bacterium.
Isethionate is specifically recognized in the periplasmic binding component, and conformational changes drive substrate passage across the membrane without direct ATP hydrolysis.
SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis.
Dias MM, King MS, Shokry E, Lilla S, Paul N, Thomason P, Zanivan S, Sumpton D, Kunji ERS, MacVicar T.
Mol Cell. 2025 Nov 6;85(21):4093-4104.e8.
doi: 10.1016/j.molcel.2025.08.018. Epub 2025 Oct 10.
PMID: 41075794.
Mitochondrial carrier protein SLC25A45 = essential for the uptake of methylated amino acids into mitochondria and for subsequent de novo biosynthesis of carnitine.
Loss-of‐function experiments in cell models => absence of SLC25A45 leads to defects in carnitine formation and mitochondrial metabolic imbalance. Structural and transport => SLC25A45 binds methylated amino acids with high affinity and mediates IM transport.
The organic cation transporters 1 and 2 mediate ethanolamine cellular efflux and control systemic phosphatidylethanolamine level.
Schubert J, Koca F, Barone F, Corona G, Ciarimboli G, Visentin M.
J Biol Chem. 2025 Nov 5:110911.
doi: 10.1016/j.jbc.2025.110911. Online ahead of print.
PMID: 41203133.
OCT1 and OCT2 mediate efflux of ethanolamine from cells, => regulation of levels of PE.
KO + transporter‐inhibition experiments => reduced ethanolamine efflux leads to elevated intracellular concentrations and altered membrane-phospholipid composition.
This mechanism influences whole-body PE homeostasis and impacts lipid metabolism in vivo.
The Proton-Activated Chloride Channel: Molecular Identification, Structure, and Role in Organelle Physiology.
Chen KH, Hagino T, Qiu Z.
Annu Rev Physiol. 2025 Nov 6.
doi: 10.1146/annurev-physiol-022724-105357. Online ahead of print.
PMID: 41197158.
Overview of the proton‑activated chloride channel (PAC/ PACC1): molecular identification, structural attributes and role in organelle physiology.
The channel is activated by acidic pH and contributes to organelle acidification, volume regulation and chloride flux.
Molecular mechanisms of the mammalian fatty acid cycle.
Gusenda C, Grininger M.
Trends Biochem Sci. 2025 Nov 7:S0968-0004(25)00223-3.
doi: 10.1016/j.tibs.2025.09.005. Online ahead of print.
PMID: 41203489.
Review on enzymatic and transporter-mediated pathways of the mammalian FA cycle, including uptake, activation, transport into organelles, β-oxidation and membrane remodelling.
Inter-dependence of MP transport proteins, metabolic enzymes and lipid-remodelling machinery.
Proposition of a unified mechanism how FA flux is co-ordinated with membrane processes.
Nanobodies: a new paradigm for brain disorder therapies.
Lafon PA, Prézeau L, Pin JP, Rondard P.
Trends Pharmacol Sci. 2025 Nov 5:S0165-6147(25)00228-7.
doi: 10.1016/j.tips.2025.10.004. Online ahead of print.
PMID: 41198506.
Perspective discussing how nanobodies are emerging as versatile tools for targeting MP receptors and transporters in the brain => new therapeutic avenues for neurological disorders.
Challenges: delivery across the blood-brain barrier, target selectivity, immunogenicity.
Membranes
Systematic membrane thickness variation across cellular organelles revealed by cryo-ET.
Glushkova D, Böhm S, Beck M.
J Cell Biol. 2026 Jan 5;225(1):e202504053. doi: 10.1083/jcb.202504053. Epub 2025 Nov 4.
PMID: 41186573.
Computational workflow to measure local membrane thickness from cryo-electron tomograms, enabling comparisons across organelles and species.
Membranes of different organelles exhibit reproducible thickness differences, and that intra-organelle variability correlates with local curvature and lipid composition.
=> Membrane thickness is not uniform but adaptively tuned in situ: functional specialization of organellar membranes.
Monitoring phospholipid dynamics in vivo with a fluorescent dye octadecyl rhodamine B.
Hao L, Zhao C, Suzuki K.
Cell Struct Funct. 2025 Oct 31.
doi: 10.1247/csf.25126. Online ahead of print.
PMID: 41183913.
octadecyl rhodamine B (R18) = lipophilic dye as a live-cell probe of phospholipid dynamics. Internalisation in yeast is dependent on PE levels.
In PE-deficient mutants R18 uptake is blocked, whereas ethanolamine supplementation restores the process: strong link between PE metabolism and R18 transport.
=> useful tool and new insights into the in vivo mobility of phospholipids and interplay between lipid metabolism and membrane transport pathways.
Viscoelastic characterization of the lipid cubic phase provides insights into high-viscosity extrusion injection for XFEL experiments.
Zabelskii D, Round E, Han H, von Stetten D, Letrun R, Kim C, Sato T, V M Melo D, de Wijn R, Kharitonov K, Smyth P, Doerner K, Kloos M, Dietze T, Morillo LL, Bean R, Round A.
Sci Rep. 2025 Nov 7;15(1):38999.
doi: 10.1038/s41598-025-25449-8.
PMID: 41203717.
Rheological analysis of LCP, a mesophase used as injection matrix in XFELs.
LCP’s viscosity and viscoelastic properties are sensitive to lipid composition and water content => guidance for optimising sample carriers for XFEL experiments involving MPs.
A subset of type 4 secretion system effectors of Brucella spp. associates to outer membrane vesicles.
Maren Ketterer, Naadir Ganief, Petra Chiquet, Adélie Lannoy, Audrey Verhaeghe, Joanne Braunweiler, Marc Dieu, Xavier De Bolle, Maxime Québatte, Christoph Dehio.
bioRxiv 2025.10.06.680763;
doi: https://doi.org/10.1101/2025.10.06.680763.
Subset of Brucella T4SS effectors are translocated into host cells but also packaged into OMVs.
These vesicle-associated effectors retain enzymatic activity and can modulate host responses independently of direct T4SS delivery.
OMV-mediated trafficking = alternative route for effector dissemination during infection.
Molecules
Peptide nanodiscs: Versatile platforms for membrane protein functional reconstitution and structural studies: A review.
Krishnarjuna B, Anantharamaiah GM, Ramamoorthy A.
Int J Biol Macromol. 2025 Nov 2:148668.
doi: 10.1016/j.ijbiomac.2025.148668. Epub ahead of print.
PMID: 41187853.
Review summarizing the development of peptide-based NDs as compact, detergent-free systems for solubilizing and studying MPs. Peptide belts derived from amphipathic sequences stabilize lipid bilayers. Authors highlight how these systems allow functional reconstitution of diverse transporters, channels, and receptors with tunable lipid environments.
Methods
Outrunning protein diffusion to the air-water interface in cryoEM.
Gusach A, Sader K, Russo CJ.
Proc Natl Acad Sci U S A. 2025 Oct 28;122(43):e2516900122.
doi: 10.1073/pnas.2516900122. Epub 2025 Oct 22.
PMID: 41123998.
This paper tackles the adsorption of proteins to the air–water interface by accelerating sample vitrification to outpace diffusion.
=> reducing the time between sample application and plunge-freezing to sub-millisecond scales prevents denaturation and preferred orientation of fragile membrane proteins.
Microfluidic control => authors demonstrate improved particle integrity and orientation distributions across several test systems.
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 pipeline developed for automatic segmentation and detection of membranes and vesicles in cryoET datasets.
Algorithm distinguishes membranes from adjacent density features, enabling HT structural annotation in tomograms.
Quantification of vesicle size, shape and connectivity.
High-throughput peptide-centric local stability assay extends protein-ligand identification to membrane proteins, tissues and bacteria.
Li K, Potel CM, Becher I, Hüttmann N, Garrido-Rodriguez M, Schwarz J, Burtscher ML, Savitski MM.
Nat Struct Mol Biol. 2025 Nov 5.
doi: 10.1038/s41594-025-01699-y. Online ahead of print.
PMID: 41193676.
HT-PELSA = high-throughput peptide-centric local stability assay that profiles protein-ligand interactions across proteomes, including MPs, tissues and bacteria.
By assessing ligand-induced changes in local peptide stability in complex lysates, the method identifies binding targets and maps binding regions without chemical modification of ligands.
Optimizing a Coarse-Grained Model for Large-Scale Membrane Protein Simulation.
Wen CY, Luo YL, Madsen JJ.
Biophys Rep (N Y). 2025 Nov 6:100238.
doi: 10.1016/j.bpr.2025.100238. Online ahead of print.
PMID: 41205699.
CG MD FFs to better capture MP conformational dynamics over microsecond scales: protein interactions, helix packing, and water permeability against atomistic simulations and experimental data, adjusting bead-type mappings and interaction strengths.
The optimized model reproduces membrane thickness and protein-embedded stability with improved computational efficiency.
Miscellaneous
‘Google Maps’ for Roman roads reveals vast extent of ancient network.
Kavanagh K.
Nature. 2025 Nov 6.
doi: 10.1038/d41586-025-03626-z. Epub ahead of print.
PMID: 41198975.
This Nature news article describes a digital mapping project that reconstructs the full network of Roman roads across Europe, North Africa, and the Middle East with unprecedented precision. Using archaeological data, historical records, and geospatial modeling, researchers built an interactive “Google Maps-like” platform visualizing how Roman routes connected cities, forts, and trade hubs over thousands of kilometers. The map reveals remarkable continuity between ancient and modern infrastructure, with many contemporary transport corridors tracing the same paths. Beyond historical curiosity, the work offers insights into the economic, cultural, and political integration achieved through Rome’s vast engineering enterprise.
Powerful new antibiotic that can kill superbugs discovered in soil bacteria.
Naddaf M.
Nature. 2025 Oct 31.
doi: 10.1038/d41586-025-03595-3. Epub ahead of print.
PMID: 41174166.
Scientists have discovered a powerful antibiotic while studying the process through which a soil bacterium naturally produces a well-known drug. The compound — called premethylenomycin C lactone — is more than 100 times more active against bacteria than the final product, antibiotic methylenomycin A, which was first identified in 1965. Tiny doses of the surprise discovery killed strains of bacteria known to cause hard-to-treat infections.
Why India’s controversial ‘cloud seeding’ trial failed to make it rain.
Basu M.
Nature. 2025 Oct 31.
doi: 10.1038/d41586-025-03555-x. Epub ahead of print.
PMID: 41174159.
An ambitious attempt by the Indian government to reduce Delhi’s toxic air pollution by inducing artificial rain has failed to trigger any precipitation. In the experiment last week, aircraft flew over the city and released particles of silver iodide and sodium chloride into the atmosphere to help water vapour to condense. Researchers say that the atmospheric conditions weren’t suitable for the experiment to succeed, but even if it had, such ‘cloud seeding’ attempts can’t solve Delhi’s pollution problem. “The obvious solution is also a boring one — clean up the sources,” says aerosol scientist Shahzad Gani.