MP

ABC transporters

Hijacking a bacterial ABC transporter for genetic code expansion. 

Iype T, Fottner M, Böhm P, Piedrafita C, Möller Y, Groll M, Lang K.

Nature. 2025 Oct 15. 

doi: 10.1038/s41586-025-09576-w. Epub ahead of print. 

PMID: 41094137.

Repurposing of a bacterial ABC transporter to import noncanonical aa for genetic code expansion inside living cells. 

Structure and bioch => shows how the transporter can be redirected without compromising membrane integrity or native function. 

By coupling transport to an orthogonal aminoacyl-tRNA synthetase system, authors incorporate designer amino acids into proteins.

Capturing transient states of heterodimeric ABC transporter TM287/288 by Time-Resolved Small-Angle X-ray Scattering.

Lea Schroeder, Dario De Vecchis, Andrey Gruzinov, Lars V. Schaefer, Clement Blanchet, Markus Seeger, Henning Tidow, and Inokentijs Josts.

bioRxiv posted 30 September 2025.

doi:10.1101/2025.09.29.679171.

Time-resolved SAXS => transient conformations of the heterodimeric ABC transporter TM287/288 during its ATPase cycle. 

Efflux pumps and secretion systems

Functional interplay between RND efflux pumps and GacS in Pseudomonas aeruginosa.

Adamiak JW, Bergen C, Ajmal L, Reddy S, Anderson PG, Rybenkov VV, Zgurskaya HI.

Appl Environ Microbiol. 2025 Sep 17;91(9):e0122325. 

doi: 10.1128/aem.01223-25. Epub 2025 Aug 18.

PMID: 40824111. 

Interplay between RND efflux pumps and the GacS sensor in P. aeruginosa. 

Genetic and phenotypic analyses => feedback between efflux activity and global regulatory circuits. 

This cross-regulation influences antibiotic tolerance, biofilm formation, and virulence traits. 

A stacked ensemble classifier for the discovery of prokaryotic efflux proteins based on sequence information.

Wang Q, Yue Q, Tao Z, Xu T, Ying J.

BMC Genomics. 2025 Sep 29;26(1):851. 

doi: 10.1186/s12864-025-12039-1.

PMID: 41023609.

Stacked ensemble classifier that predicts prokaryotic efflux proteins from sequence features. 

Training on curated datasets improves recall across diverse families. Feature importance highlights transmembrane topology and conserved motifs as key signals.

Structural and functional analysis of the Mycobacterium tuberculosis MmpS5L5 efflux pump presages increased bedaquiline resistance.

Fountain AJ, Böhning J, McLaughlin SH, Morgan TE, Edelstein PH, Troll M, Lamers MH, Bharat TAM, Luisi BF, Ramakrishnan L.

Proc Natl Acad Sci U S A. 2025 Sep 30;122(39):e2516660122. 

doi: 10.1073/pnas.2516660122. Epub 2025 Sep 23.

PMID: 40986343.

Structure function analyses of the MmpS5–MmpL5 efflux system from Mycobacterium tuberculosis linked to bedaquiline resistance. 

Cryo-EM and biochemistry => assembly and transport pathway (+ mutations that elevate D efflux). 

Fitness and susceptibility assays => connection of specific substitutions to increased MICs. 

MmpL12 transports lipooligosaccharides and impacts virulence in Mycobacterium marinum.

Bailo R, Kumar CMS, Singh A, Lund PA, Bavro VN, Bhatt A.

Microbiology (Reading). 2025 Oct;171(10). 

doi: 10.1099/mic.0.001618.

PMID: 41060696.

MmpL12 as a transporter of lipooligosaccharides in Mycobacterium marinum. 

Loss-of-function and complementation experiments => altered cell envelope composition and attenuated virulence. 

Biochemical assays => substrate preference and export activity for defined glycolipids. 

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 Oct 11:169485. 

doi: 10.1016/j.jmb.2025.169485. Online ahead of print.

PMID: 41083144.

MD + experiments to dissect the CLD (C-terminal linker domain) dynamics in HlyA, the E. coli type I secretion toxin. 

Authors show how CLD flexibility coordinates substrate recruitment to the T1SS machinery. 

Mutational perturbations of dynamic hotspots alter secretion efficiency and toxicity. 

LPS transport

Conformational Plasticity of LptC Regulates Lipopolysaccharide Transport by the LptB2FGC Complex. 

Klausnitzer A, Kaur J, Rath T, Seidl S, Becker-Baldus J, Morgner N, Glaubitz C.

J Am Chem Soc. 2025 Sep 20. 

doi: 10.1021/jacs.5c11923. Epub ahead of print. 

PMID: 40974309.

NMR and MS => LptC undergoes conformational changes that tune LPS transport by the LptB2FGC complex. 

Specific states of LptC modulate ATPase activity and lipid efficiency. 

Crosslinking and dynamics => identification of interfaces coordinating periplasmic bridge assembly. 

High-Throughput Identification and Characterization of LptDE-Binding Bicycle Peptides Using Phage Display and Cryo-EM.

Allyjaun S, Dunbar E, Hardwick SW, Newell S, Holding F, Rowland CE, St Denis MA, Pellegrino S, Arruda Bezerra G, Bournakas N, Chirgadze DY, Cooper L, Paris G, Lewis N, Brown P, Skynner MJ, Dawson MJ, Beswick P, Hubbard J, van den Berg B, Newman H.

J Med Chem. 2025 Oct 23;68(20):21144-21155. 

doi: 10.1021/acs.jmedchem.5c00307. Epub 2025 Oct 6.

PMID: 41048016.

HT phage display platform => bicyclic peptides that bind the LptDE OM complex. 

Cryo-EM structures of peptide-LptDE complexes reveal binding modes that block LPS insertion. 

Medicinal chemistry optimization => ligands with improved affinity and bacterial OM permeability => starting points for antibiotics targeting LPS assembly.

BAM and OM biogenesis:

Structure of a distinct β-barrel assembly machinery complex in the Bacteroidota.

Silale A, Madej M, Mikruta K, Frey AM, Hart AJ, Baslé A, Scavenius C, Enghild JJ, Trost M, Hirt RP, van den Berg B.

Nat Microbiol. 2025 Oct 1. 

doi: 10.1038/s41564-025-02132-2. Online ahead of print.

PMID: 41034344.

Authors describe a distinct β-barrel assembly machinery (BAM-like) complex in Bacteroidota with unique subunit composition. 

Structural analyses => divergent mechanism for folding and inserting OM proteins. 

Functional assays => essentiality for envelope integrity and species-specific substrate selection.

A protein antibiotic inhibits the BAM complex to kill without cell entry.

Fabian Munder, Matthew Johnson, Imogen Samuels, Laura McCaughey, Oleksii Zdorevskyi, Chunxiao Wang, Ashleigh Kropp, Lauren Zavan,  Erin P. Price,  Derek S. Sarovich, Swati Varshney, Christopher McDevitt, Hari Venugopal, Vivek Sharma, Matthew T. Doyle, Francesca Short, Debnath Ghosal, James P. R. Connolly, Gavin J. Knott, Rhys Grinter.

https://www.biorxiv.org/content/10.1101/2025.09.18.677229v1

Cryo-EM structure of Pseudomonas aeruginoas BAM complex in complex with pyocin L1 and L2 -> Pyocin binds to extracellular loop 6 of BamA and deploy its C-terminal peptide in the barrel lumen to interact with strand beta 1, inhibiting OM biogenesis and killing cells. Transposon mutagenesis -> genes involved in sensitivity/tolerance to pyocins. Transcriptomic/proteomic analysis -> consequences of pyocin treatment on cell physiology. CryoET -> Pyocin treatment leads to OM loss of integrity (holes, gaps, blebbing, release of vesicle).

Molecular insights into how the motions of the β-barrel and POTRA domains of BamA are coupled for efficient function.

Csoma N, Machin JM, Whitehouse JM, Rodrìguez-Alonso R, Olejnik M, Cahill AK, Cho SH, Schäberle TF, Iorga BI, Ranson NA, Radford SE, Calabrese AN, Collet JF.

Nat Commun. 2025 Oct 3;16(1):8832. 

doi: 10.1038/s41467-025-63897-y.

PMID: 41044071. 

BamA’s β-barrel and POTRA domains couple motions for efficient OM protein assembly. 

Structural dynamics and biophysical assays => interdomain communication pathways. 

Mutations that uncouple motions impair BAM activity.

Structure-function relationship of the Pseudomonas aeruginosa AsmA-like proteins YhdP and YdbH involved in outer membrane biogenesis. 

Sposato D, Pederzoli C, Bufano M, Sciò P, Rossi L, Leoni L, Rampioni G, Visca P, Coluccia A, Imperi F.

Protein Sci. 2025 Oct;34(10):e70227. 

doi: 10.1002/pro.70227. 

PMID: 40970438.

Study on YhdP and YdbH in P. aeruginosa and their roles in OM biogenesis. 

Structure-function studies link conserved motifs to lipid transport and OM integrity. 

Deletions sensitize cells to envelope stress and antibiotics. 

The work refines models of intermembrane lipid trafficking in Gram-negatives.

Insights into the complex formation of a trimeric autotransporter adhesin with a peptidoglycan-binding periplasmic protein.

Yoshimoto S, Sasahara J, Suzuki A, Kanie J, Koiwai K, Lupas AN, Hori K.

Cell Surf. 2025 Sep 29;14:100155. 

doi: 10.1016/j.tcsw.2025.100155. eCollection 2025 Dec.

PMID: 41103730. 

Complex formation between a trimeric autotransporter adhesin and a periplasmic PG-binding partner. 

Biophysics and microscopy => the periplasmic protein scaffolds adhesin assembly and cell-surface presentation.

Ion pumps, channels and rhodopsins:

Important amino acid residues in the chloride pump halorhodopsin that accelerate ion transport despite no direct interaction with the substrate.

Zhai Y, Shimosaka A, Tsukamoto T, Kikukawa T.

J Biol Chem. 2025 Sep 11:110703. 

doi: 10.1016/j.jbc.2025.110703. Online ahead of print.

PMID: 40945730.

identification of amino-acid residues in halorhodopsin that accelerate chloride pumping without directly contacting the ion. 

Spectroscopic and kinetic analyses => these residues shape the protein’s energy landscape and photocycle timing. 

Mutations shift intermediate lifetimes and transport turnover = remote control of catalysis. 

The findings underscore allosteric tuning of ion pumps beyond the primary binding site.

Light-Powered Transport of Organic Anions by Microbial Rhodopsins.

Shen S, Akita S, Wada J, Eguchi M, Tsukamoto T, Jung KH, Sudo Y, Kikukawa T.

J Phys Chem Lett. 2025 Oct 2:10528-10535. 

doi: 10.1021/acs.jpclett.5c02551. Online ahead of print.

PMID: 41039638.

Light-driven transport of organic anions by microbial rhodopsins. Spectroscopic and electrophysiological => substrate scope and pumping stoichiometry. 

Mutational analysis => identification of residues tuning selectivity and kinetics. Towards optogenetic control of metabolite flux ?

Targeting prokaryotic ion channel by a chimera of fluorescent protein and artificial peptide toxin.

Iunusova VA, Orlov NA, Nekrasova OV, Feofanov AV, Vassilevski AA, Kuzmenkov AI.

Biochim Biophys Acta Biomembr. 2025 Sep 11:184458. 

doi: 10.1016/j.bbamem.2025.184458. Online ahead of print.

PMID: 40945561.

Fluorescent protein/toxin chimera that targets a prokaryotic ion channel. 

=> visualization and functional inhibition of the channel in living bacteria. 

Electrophysiology confirms selective pore blockade and altered membrane potential.

Small angle neutron scattering study of rhodopsin oligomerization and G-protein coupling in a physiologically relevant lipid membrane.

Soubias O, Nickels JD, Hines KG, Teague WE, Northup JK, Katsaras J, Gawrisch K.

Biochim Biophys Acta Biomembr. 2025 Sep 11:184454. 

doi: 10.1016/j.bbamem.2025.184454. Online ahead of print.

PMID: 40945563 Review.

SANS => oligomeric organization of rhodopsin in lipid membranes that mimic native composition = correlates oligomer states with G-protein coupling propensities. 

Changes in lipid packing and protein density tune receptor interactions and signaling efficiency.

Secondary-active, small molecule transporters & plant transport:

Elucidation of the structure and molecular mechanisms of the aspartate antiporter.

Nanatani K, Guan L, Kanno R, Kawabata T, Watanabe S, Katsube S, Hariharan P, Hidaka M, Yamanaka T, Toda K, Fujiki T, Kunii K, Miyamoto A, Chiba F, Ogasawara S, Murata T, Inaba K, Mitsuoka K, Abe K, Yamamoto M, Koshiba S.

Commun Biol. 2025 Sep 25;8(1):1359. 

doi: 10.1038/s42003-025-08676-7.

PMID: 40998974.

Structure of an aspartate : proton antiporter => transport mechanism. 

Alternating-access conformations reveal gating residues and substrate coordination sites. 

Functional reconstitution and mutational analysis validate proton coupling and selectivity determinants.

Cryo-EM structure and dynamic basis of phosphate uptake by PHT1 in rice.

Du Z, Guan Z, Liu H, Zhang J, He H, Zheng Z, Zhang W, Jiang L, Zuo J, Liu Y, Wan B, Tu H, Dong F, Lai X, Xiong L, Yin P, Xue S, Chen Y, Liu Z.

Dev Cell. 2025 Sep 25:S1534-5807(25)00541-6. 

doi: 10.1016/j.devcel.2025.09.003. Online ahead of print.

PMID: 41005295.

Cryo-EM structures of the rice phosphate transporter PHT1 in multiple functional states. 

Structures + dynamics analyses => conformational transitions and key residues governing substrate recognition and gating. 

Electrophysiology and mutagenesis => mechanistic model for proton-coupled phosphate uptake.

Membrane transporters in Plants: Key players in abiotic and biotic stress tolerance and nutritional transport.

Sharma R, Kumar D, Parkirti P, Singh A, Sharma A, Langeh K, Singh A, Sharma M, Mir NR, Khajuria A, Kapoor N, Bhardwaj R, Ohri P.

Plant Physiol Biochem. 2025 Oct;227:110084. 

doi: 10.1016/j.plaphy.2025.110084. Epub 2025 May 26.

PMID: 40449185.

Review on plant membrane transporters: nutrient uptake and stress tolerance. 

Genomic, structural, and physiological data to highlight key transporter families + regulatory networks and cross-talk under abiotic and biotic stresses + emerging biotechnological strategies to manipulate transport for crop improvement.

Eukaryotes, organelles, structural cell biology:

Nir2 crystal structures reveal a phosphatidic acid-sensing mechanism at ER-PM contact sites.

Kim D, Lee S, Jun Y, Lee C.

Proc Natl Acad Sci U S A. 2025 Oct 28;122(43):e2516849122. 

doi: 10.1073/pnas.2516849122. Epub 2025 Oct 23.

PMID: 41129229.

Crystal structures of Nir2 => phosphatidic-acid sensing mechanism at ER–plasma-membrane contact sites. 

Lipid-binding pockets and conformational changes explain recruitment and lipid transfer. 

Disruption of PA sensing => impairment of contact-site functions in cells.

Cryo-EM structure of the human Derlin-1/p97 complex reveals a hexameric channel in ERAD.

Wang Q, Yao D, Rao B, Xia Y, Li W, Li S, Cao M, Shen Y, Qin A, Cao Y.

Commun Biol. 2025 Oct 17;8(1):1481. 

doi: 10.1038/s42003-025-08880-5.

PMID: 41107410. 

Cryo-EM structure of a human Derlin-1/p97 complex forming a hexameric transmembrane channel central to ERAD. 

The architecture shows how Derlin-1 engages p97 to couple ATPase cycles with substrate extraction. 

Mutations => pore-lining residues involved in polypeptide movement across the ER membrane = clarifies an elusive step in clearing misfolded secretory proteins.

Visualization of lysosomal membrane proteins by cryo electron tomography.

McVeigh BM, De Jesús-Pérez JJ, Siepe DH, Gogoi P, Mageswaran SK, Kalocsay M, Mihelc EM, Moiseenkova-Bell VY.

Nat Commun. 2025 Oct 17;16(1):9234. 

doi: 10.1038/s41467-025-64314-0.

PMID: 41107240. 

Cryo-ET to visualize lysosomal MPs in their native organellar context. Subtomogram averaging => architectures for transporters and channels embedded in the crowded lysosomal membrane. 

Luminal and cytosolic features: organization principles and protein /protein contacts that correlate with function.

In situ structure determination of Respiratory Supercomplexes and ATP synthase oligomers in mammalian mitochondrial inner membrane.

Atsuki Nakano, Takahiro Masuya, Shinsuke Akisada, Moe Ishikawa-Fukuda, Kaoru Mitsuoka, Hideto Miyoshi, Masatoshi Murai, Ken Yokoyama.

bioRxiv 2025.09.19.677273.

doi: https://doi.org/10.1101/2025.09.19.677273.

In situ cryo-ET resolves respiratory supercomplexes and ATP synthase oligomers within mammalian cristae => native assemblies, their spatial arrangements, and local curvature coupling. 

Structural variability <=> dynamic organization tuned to metabolic state.

Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor.

Zhang L, Mobbs JI, Bennetts FM, Venugopal H, Nguyen ATN, Christopoulos A, van der Es D, Heitman LH, May LT, Glukhova A, Thal DM.

Nat Commun. 2025 Aug 18;16(1):7674. 

doi: 10.1038/s41467-025-62872-x.

PMID: 40825947. 

Cryo-EM + pharmacology + mutagenesis => ligand binding and activation at the human A3 adenosine receptor. 

Structures with agonists and modulators map conformational pathways to G-protein engagement. 

Biophysical assays quantify efficacy determinants and allosteric coupling.

Concepts, energetics & biophysics perspectives:

Quantification of Membrane Protein Conformational Free Energy from Mutations and a Single Atom.

Ramirez-Cordero B, Traaseth NJ.

J Am Chem Soc. 2025 Sep 15. 

doi: 10.1021/jacs.5c04065. Online ahead of print.

PMID: 40953491.

Conformational free energies of MPs from mutational scans and a strategically placed single atom probe. 

NMR + computation => local stability contributions in a lipid environment. 

The method maps energy landscapes across folds and states. 

This approach enables comparative energetics and rational stabilization of MPs.

Packing of apolar amino acids is not a strong stabilizing force in transmembrane helix dimerization.

Loiseau GJ, Senes A.

Biophys J. 2025 Sep 25:S0006-3495(25)00616-2. 

doi: 10.1016/j.bpj.2025.09.036. Online ahead of print.

PMID: 41013893.

Model helix dimers => tight packing of apolar side chains is not the dominant stabilizing force in transmembrane dimerization. This challenges assumptions drawn from soluble proteins.

Instead, context-dependent factors like helix geometry and specific motifs play larger roles. 

Biophysical measurements decouple van der Waals contact from association propensity. 

Correlating membrane-protein dynamics with function: Integrating bioinformatics, molecular dynamics, and single-molecule FRET.

Higinbotham HR, Arbour CA, Imperiali B.

Protein Sci. 2025 Nov;34(11):e70352. 

doi: 10.1002/pro.70352.

PMID: 41131924.

Bioinformatics + MD + sm FRET to relate membrane-protein dynamics to function. 

Miscellaneous

Olfactory floral mimicry of injured ants mediates the attraction of kleptoparasitic fly pollinators. 

Mochizuki K.

Curr Biol. 2025 Sep 24:S0960-9822(25)01126-1. 

doi: 10.1016/j.cub.2025.08.060. Epub ahead of print. 

PMID: 40997806.

A species of Japanese dogbane (Vincetoxicum nakaianum) mimics the odour of injured ants to tempt the flies that feed on the insects to pollinate them. Botanist Ko Mochizuki noticed that flies were attracted to dogsbane, and found that the plant produces several scented chemicals that are also in ants’ pheromone SOS calls to their nestmates — the first evidence of plants copying ants.

World’s first AI-designed viruses a step towards AI-generated life.

Kavanagh K.

Nature. 2025 Sep 19. 

doi: 10.1038/d41586-025-03055-y. Epub ahead of print. 

PMID: 40973752.

Scientists used artificial intelligence to write coherent viral genomes, using them to synthesize bacteriophages capable of killing resistant strains of bacteria.

The ‘near-telepathic’ device that puts AI in your head. 

Simms C.

Nature. 2025 Sep 18. 

doi: 10.1038/d41586-025-03000-z. Epub ahead of print. 

PMID: 40968287.

A wearable device offers a similar experience to brain-computer interfaces without the invasive implants or the privacy concerns that come along with mind-reading. The ‘AlterEgo’ device detects electrical signals in the muscles used to formulate speech that are sent by the brain when you silently mouth or even just internally articulate words. Its makers say it could be used by people who have issues with speaking, or to interact with voice-controlled applications without having to talk out loud.