MP
Structures and mechanism of the human mitochondrial pyruvate carrier.
Liang J, Shi J, Song A, Lu M, Zhang K, Xu M, Huang G, Lu P, Wu X, Ma D.
Nature. 2025 May;641(8061):258-265.
doi: 10.1038/s41586-025-08873-8. Epub 2025 Mar 18.
PMID: 40101766.
High-resolution cryo-EM structures of the human mitochondrial pyruvate carrier in multiple functional states.
=> MPC = heterodimer with central substrate-binding cavity + lateral gate for substrate entry.
IF -OF with alternating-access transport mechanism.
Disease mutations and inhibitor binding sites are mapped.
Structure of mitochondrial pyruvate carrier and its inhibition mechanism.
He Z, Zhang J, Xu Y, Fine EJ, Suomivuori CM, Dror RO, Feng L.
Nature. 2025 May;641(8061):250-257.
doi: 10.1038/s41586-025-08667-y. Epub 2025 Mar 5.
PMID: 40044865.
cryo-EM structures of the human MPC alone + bound to a known inhibitor.
=> dynamic architecture that toggles between IF and OF.
=> Inhibitor binding => lock in an IF.
Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier.
Sichrovsky M, Lacabanne D, Ruprecht JJ, Rana JJ, Stanik K, Dionysopoulou M, Sowton AP, King MS, Jones SA, Cooper L, Hardwick SW, Paris G, Chirgadze DY, Ding S, Fearnley IM, Palmer SM, Pardon E, Steyaert J, Leone V, Forrest LR, Tavoulari S, Kunji ERS.
Sci Adv. 2025 Apr 18;11(16):eadw1489.
doi: 10.1126/sciadv.adw1489. Epub 2025 Apr 18.
PMID: 40249800.
Structural, biochemical, and simulation => study how MPC binds and transports pyruvate.
Critical residues for substrate and inhibitor interactions are idendified, with Nb-stabilized cryo-EM structures capturing different conformational states.
In situ structure and assembly of the ABC-type tripartite pump MacAB-TolC.
Huo T, Zhang W, Yu Z, Zheng W, Wu Y, Ren Q, Wan Z, Cao J, Wang Z, Shi X.
Commun Biol. 2025 Jun 3;8(1):848.
doi: 10.1038/s42003-025-08236-z.
PMID: 40461577.
in situ cryo-EM => assembly of the MacAB-TolC pump in Gram-negative bacteria, directly visualized in the membrane !!! in the presence or in the absence of erythromycin.
The in situ assembly process of MacAB-TolC starts from the formation of MacA-TolC subcomplex, and then flexible binding of MacB in the presence of an antibiotic substrate.
Engineering of soluble bacteriorhodopsin.
Nikolaev A, Orlov Y, Tsybrov F, Kuznetsova E, Shishkin P, Kuzmin A, Mikhailov A, Nikolaeva YS, Anuchina A, Chizhov I, Semenov O, Kapranov I, Borshchevskiy V, Remeeva A, Gushchin I.
Chem Sci. 2025 May 13.
doi: 10.1039/d5sc02453f. Online ahead of print.
PMID: 40406218.
Bacteriorhodopsin reengineered to be water-soluble while retaining its proton-pumping activity (introduction of mutations to increase solubility without compromising structural stability or photoreactivity).
Enhanced secretion through type 1 secretion system by grafting a calcium-binding sequence to modify the folding of cargo proteins.
Uehara R, Kamiya Y, Maeda S, Okamoto K, Toya S, Chiba R, Amesaka H, Takano K, Matsumura H, Tanaka SI.
Protein Sci. 2025 Jun;34(6):e70165.
doi: 10.1002/pro.70165.
PMID: 40384617.
Introduction of a calcium-binding sequence into cargo proteins to modulate folding during type 1 secretion => enhances proper folding and increases secretion efficiency.
Promising tool for recombinant protein production.
The structure and function of the ghrelin receptor coding for drug actions.
Shiimura Y, Im D, Tany R, Asada H, Kise R, Kurumiya E, Wakasugi-Masuho H, Yasuda S, Matsui K, Kishikawa JI, Kato T, Murata T, Kojima M, Iwata S, Masuho I.
Nat Struct Mol Biol. 2025 Mar;32(3):531-542.
doi: 10.1038/s41594-024-01481-6. Epub 2025 Jan 20.
PMID: 39833471.
Structural analysis of the ghrelin receptor with agonists and antagonists
=> distinct active and inactive conformations. Key interactions between ligand and binding pocket are identified.
=> explains how different compounds modulate signaling in this metabolic GPCR.
Molecular basis of the functional conflict between chloroquine and peptide transport in the Malaria parasite chloroquine resistance transporter PfCRT.
Tanner JD, Richards SN, Corry B.
Nat Commun. 2025 Mar 27;16(1):2987.
doi: 10.1038/s41467-025-58244-0.
PMID: 40140375.
Article exploring how PfCRT transports both chloroquine and peptides, leading to functional conflict. Structural modeling and in vitro tests.
Dual substrate interaction underlies drug inefficacy.
Antibiotics-induced conformational heterogeneity of a multidrug transporter revealed by single-molecule FRET.
Hassan R. Maklad, Tom Kache, Aurelie Roth, Maria Mamkaeva, Cedric Govaerts, Jelle Hendrix, and Chloe Martens.
bioRxiv posted 22 May 2025.
doi:10.1101/2025.05.17.654648
sm-FRET => conformational heterogeneity in a multidrug transporter in response to antibiotics.
Different antibiotics stabilize different conformations, affecting the transport cycle. The data support a dynamic model involving multiple coexisting states.
Molecular mechanism of substrate transport by human peroxisomal ABCD3.
Meghna Gupta, Nitesh Kumar Khandelwal, Devin John Seka, Sree Ganesh Balasubramani, Miles Sasha Dickinson, Alexander Myasnikov, Ignacia Echeverria, and Robert M Stroud.
bioRxiv posted 27 May 2025.
doi:10.1101/2025.05.21.655323.
Description of the structure and transport mechanism of human peroxisomal transporter ABCD3.
Key motifs for substrate recognition and conformational transitions are identified. ATP-driven conformational changes are captured by cryo-EM.
Substrate-induced assembly and functional mechanism of the bacterial membrane protein insertase SecYEG-YidC.
Max Busch, Cristian Rosales Hernandez, Michael Kamel, Yulia Schaumkessel, Eli van der Sluis, Otto Berninghausen, Thomas Becker, Roland Beckmann, and Alexej Kedrov.
bioRxiv posted 27 May 2025.
doi:10.1101/2025.05.26.656142.
Study showing that substrate presence induces assembly of the SecYEG-YidC insertase complex.
Cryo-EM => YidC stabilizes SecYEG for peptide insertion. Complex formation is conditional upon substrate binding.
Allosteric Control of Super-Agonism in a Ligand-Gated Ion Channel.
Franco Viscarra, Teresa Minguez, Isabel Bermudez-Diaz, and Philip C Biggin.
bioRxiv posted 25 May 2025.
doi:10.1101/2025.05.23.655750.
Simulations and mutagenesis to identify how distant residues modulate gating in a GLIC.
=> mechanisms of super-agonism through allosteric pathways.
=> data-driven model describes transitions between closed, open, and hyperactive states.
A Structural Mechanism for Noncanonical GPCRSignal Transduction in the Hedgehog Pathway.
William P. Steiner, Nathan Iverson, Guibing Liu, Varun Venkatakrishnan, Jian Wu, Tomasz Maciej Stepniewski, Zachary Michaelson, Jan Broeckel, Ju-Fen Zhu, Jessica Bruystens, Annabel Lee, Isaac Nelson, Daniela Bertinetti, Corvin D. Arveseth, Gerald Tan, Paul Spaltenstein, Jiewei Xu, Ruth Huttenhain, Michael Kay, Friedrich W. Herberg, Jana Selent, Ganesh S. Anand, Roland L. Dunbrack, Jr, Susan S. Taylor, and Benjamin R. Myers.
bioRxiv posted 27 May 2025.
doi:10.1101/2024.10.31.621410.
Description of a noncanonical GPCR mechanism in Hedgehog signaling, lacking classic G-protein coupling.
Structural analysis => novel interactions with intracellular effectors.
=> Alternative allosteric model is proposed for cellular signaling.
Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate K+-Cl- cotransporters.
Fudo S, Verkhovskaya M, Di Scala C, Rivera C, Kajander T.
FEBS Open Bio. 2025 Jun 13. doi: 10.1002/2211-5463.70063. Online ahead of print.
PMID: 40509965
Characterization of invertebrate K⁺/Cl⁻ cotransporters using cellular and proteoliposome assays.
=> quantification of ion kinetics, affinity, and allosteric regulation.
Reconstitution experiments highlight the mechanistic diversity across species. This contributes to understanding ionic regulation evolution.
The solute carrier superfamily interactome.
Frommelt F, Ladurner R, Goldmann U, Wolf G, Ingles-Prieto A, Lineiro-Retes E, Gelová Z, Hopp AK, Christodoulaki E, Teoh ST, Leippe P, Santini BL, Rebsamen M, Lindinger S, Serrano I, Onstein S, Klimek C, Barbosa B, Pantielieieva A, Dvorak V, Hannich TJ, Schoenbett J, Sansig G, Mocking TAM, Ooms JF, IJzerman AP, Heitman LH, Sykacek P, Reinhardt J, Müller AC, Wiedmer T, Superti-Furga G.
Mol Syst Biol. 2025 Jun;21(6):632-675.
doi: 10.1038/s44320-025-00109-1. Epub 2025 May 12.
PMID: 40355756
Systematic study to map protein-protein interactions across SLCs.
High-throughput proteomics => identification of functional clusters and novel associations. The network reveals extensive metabolic coordination and druggable nodes.
Membranes
Magnetically Controlled Polymer Giant Unilamellar Vesicles.
Abdollahi N, Messmer D, Mihali V, Palivan CG.
Small. 2025 Jun 1:e2502552.
doi: 10.1002/smll.202502552. Online ahead of print.
PMID: 40451750.
Design of magnetically responsive GUVs using specialized polymers: vesicles can be guided and manipulated in aqueous environments.
=> platforms for targeted delivery or synthetic biology interfaces.
Mechanism for Vipp1 spiral formation, ring biogenesis, and membrane repair.
Naskar S, Merino A, Espadas J, Singh J, Roux A, Colom A, Low HH.
Nat Struct Mol Biol. 2025 Mar;32(3):571-584. doi: 10.1038/s41594-024-01401-8. Epub 2024 Nov 11.
PMID: 39528797.
Cyanobacterial protein Vipp1 assembles into spirals and rings reminiscent of ESCRT-III complexes.
Cryo-EM and structural analysis => Vipp1 forms helical polymers that can generate and stabilize membrane curvature. The assembly is driven by GTP binding and regulated by membrane tension and curvature.
Shows how Vipp1 contributes to thylakoid membrane repair and remodeling in photosynthetic organisms.
The cyanobacterial protein VIPP1 forms ESCRT-III-like structures on lipid bilayers.
Pan S, Gries K, Engel BD, Schroda M, Haselwandter CA, Scheuring S.
Nat Struct Mol Biol. 2025 Mar;32(3):543-554. doi: 10.1038/s41594-024-01367-7. Epub 2024 Jul 26.
PMID: 39060677;
High-resolution microscopy and biophysical assays to demonstrate that VIPP1 forms dynamic filaments and helical tubes on model membranes.
These structures closely resemble those formed by eukaryotic ESCRT-III proteins during membrane scission. The study also shows that VIPP1 polymerization is sensitive to membrane curvature and tension.
Conserved strategy for membrane remodeling from bacteria to eukaryotes.
A quantitative analysis of ligand binding at the protein-lipid bilayer interface.
Barkdull AP, Holcomb M, Forli S.
Commun Chem. 2025 Mar 22;8(1):89. doi: 10.1038/s42004-025-01472-8.
PMID: 40121339.
Computational and biophysical framework to quantify how ligands interact with proteins at membrane interfaces.
MD with free energy calculations to analyze ligand affinity across various lipid environments.
=> membrane composition and protein conformational dynamics significantly influence binding thermodynamics.
Methods
Generation of Conformation-Specific Monoclonal Antibodies for Integral Membrane Proteins.
Sheldon N, Dhandapani G, Kim J, Spangler CJ, Fang C, Park J, Rao P, Gouaux E.
Curr Protoc. 2025 May;5(5):e70142.
doi: 10.1002/cpz1.70142.
PMID: 40418540.
Protocol for developing monoclonal antibodies that specifically recognize different conformational states of integral MPs. Using stabilized antigens and hybridoma screening, they isolate antibodies that can discriminate between active and inactive forms.
Applicable to transporters, receptors, and ion channels.
MDTAP: a tool to analyze permeation events across membrane proteins.
Sundaresan S, Raghuvamsi PV, Rathinavelan T.
Bioinform Adv. 2025 May 12;5(1):vbaf102.
doi: 10.1093/bioadv/vbaf102. eCollection 2025.
PMID: 40421423.
MDTAP = new computational pipeline for detecting and characterizing solute permeation events through membrane channels in molecular simulations.
=> detailed tracking of translocation events (dwell times, permeation paths, and energy barriers).
Controlling lipid droplet dynamics via tether condensates.
Amari C, Simon D, Pasquier E, Bellon T, Plamont MA, Souquere S, Pierron G, Salvaing J, Thiam AR, Gueroui Z.
Nat Chem Biol. 2025 May 21.
doi: 10.1038/s41589-025-01915-2. Epub ahead of print.
PMID: 40399584.
Identification of protein condensates that tether lipid droplets to the endoplasmic reticulum and regulate their movement and growth.
Optogenetics and live-cell imaging => authors show that condensate formation is reversible and modulates lipid exchange.
The tethering mechanism involves phase separation of specific scaffold proteins.
SPITROBOT-2 advances time-resolved cryo-trapping crystallography to under 25 ms.
Maria Spiliopoulou, Caitlin E. Hatton, Martin Kollewe, Jan-Philipp Leimkohl, Hendrik Schikora, Friedjof Tellkamp, Pedram Mehrabi, and Eike C. Schulz.
bioRxiv posted 25 May 2025.
doi:10.1101/2025.05.23.655289.
SPITROBOT-2 = next-generation device enabling ultrafast time-resolved crystallography with cryo-trapping at sub-25 millisecond timescales.
Demonstrated on model enzymes (xylose isomerase, human insulin and bacteriophage T4 lysozyme) => transient conformational states previously inaccessible.
Monitoring the Coating of Single DNA Origami Nanostructures with a Molecular Fluorescence Lifetime Sensor.
Michael Scheckenbach, Gereon Andreas Brueggenthies, Tim Schroeder, Karina Betuker, Lea M. Wassermann, Philip Tinnefeld, Amelie Heuer-Jungemann, and Viktorija Glembockyte.
bioRxiv posted 27 May 2025.
doi:10.1101/2024.10.28.620667.
Fluorescence lifetime-based sensor to monitor the coating of DNA origami with individual molecular layers in real time.
Enables single-particle tracking of surface modifications without need for ensemble averaging.
Dissecting Large-Scale Structural Transitions in Membrane Transporters Using Advanced Simulation Technologies.
Pant S, Dehghani-Ghahnaviyeh S, Trebesch N, Rasouli A, Chen T, Kapoor K, Wen PC, Tajkhorshid E.
J Phys Chem B. 2025 Mar 18.
doi: 10.1021/acs.jpcb.5c00104. Online ahead of print.
PMID: 40100959.
Enhanced molecular simulations to map the conformational landscapes of membrane transporters during their functional cycles.
Adaptive sampling and Markov models to capture transitions between key intermediate states.
=> reveal coordinated domain motions and energy barriers associated with substrate transport.
Microbio
Growth rates of bacteria in vivo.
Stewart PS.
Trends Microbiol. 2025 May 15:S0966-842X(25)00143-X.
doi: 10.1016/j.tim.2025.04.014. Epub ahead of print.
PMID: 40379576.
Review examining methods for measuring bacterial growth rates within host environments, emphasizing non-culture-based approaches (comparison of metabolic labeling, stable isotope probing, and genomic sequencing methods).
In vivo growth rates are often slower and more heterogeneous than in vitro conditions.
Unlocking antimicrobial resistance with multiomics and machine learning.
Ghosh A, Vang CK, Brenner EP, Ravi J.
Trends Microbiol. 2025 May 26:S0966-842X(25)00146-5.
doi: 10.1016/j.tim.2025.04.017. Online ahead of print.
PMID: 40425396.
Discusses how integrated multiomics data combined with ML can decipher AMR mechanisms.
Case studies highlight the power of AI in unraveling complex AMR networks.
Antimicrobial efflux and biofilms: an interplay leading to emergent resistance evolution.
Vareschi S, Jaut V, Vijay S, Allen RJ, Schreiber F.
Trends Microbiol. 2025 May 22:S0966-842X(25)00123-4.
doi: 10.1016/j.tim.2025.04.012. Epub ahead of print.
PMID: 40410028.
Study how efflux pump activity and biofilm formation jointly contribute to AMR.
Biofilm-associated gradients and cellular heterogeneity are suggested to amplify the role of efflux in survival. This interplay creates a feedback loop that promotes resistance evolution.
Miscellaneous
These contact lenses give people infrared vision – even with their eyes shut.
Gibney E.
Nature. 2025 May 22.
doi: 10.1038/d41586-025-01630-x. Epub ahead of print.
PMID: 40404969.
Researchers have made contact lenses that give people infrared vision — even with their eyes closed. The lenses are infused with nanoparticles that convert near-infrared light into shorter-wavelength light that humans can see. The result is multi-coloured infrared images that contrast with the monochrome of night-vision goggles. But the lenses don’t amplify light like goggles do, so the infrared light has to be quite bright to be visible.
Computer-Aided Drug Discovery for Undruggable Targets.
Sun Q, Wang H, Xie J, Wang L, Mu J, Li J, Ren Y, Lai L.
Chem Rev. 2025 May 27.
doi: 10.1021/acs.chemrev.4c00969. Epub ahead of print.
PMID: 40423592.
This comprehensive review outlines recent advances in computational tools for targeting proteins traditionally deemed “undruggable”. Techniques include structure-based design, molecular docking, and AI-driven virtual screening. The authors emphasize strategies for addressing flexible, disordered, or shallow binding sites. These innovations are expanding the scope of drug discovery into previously inaccessible biological space.
Advancing Covalent Ligand and Drug Discovery beyond Cysteine.
Kim G, Grams RJ, Hsu KL.
Chem Rev. 2025 May 22.
doi: 10.1021/acs.chemrev.5c00001. Epub ahead of print.
PMID: 40404146.
Review highlighting new strategies for covalent drug design that target amino acids other than cysteine, such as lysine, serine, tyrosine, and histidine.
It discusses advances in reactive warheads, chemoproteomics, and structure-guided design to broaden the ligandable proteome.
The MICrONS Project: biggest brain map ever details huge number of neurons and their activity.
Naddaf M.
Nature. 2025 Apr 9.
doi: 10.1038/d41586-025-01088-x. Epub ahead of print.
PMID: 40205110.
An unprecedented dataset of high resolution anatomical images of individual cells in mouse visual cortex, mapped on to their responses. This integrated view of function and structure lays a foundation for discovering the computational bases of cortical circuits.
The map is the result of the Machine Intelligence from Cortical Networks (MICrONS) project, who described their work in a package of eight papers published in Nature and Nature Methods.
Buckle up for an amazing journey here:
https://www.nature.com/immersive/d42859-025-00001-w/index.html !!!
Cells are swapping their mitochondria. What does this mean for our health?
Conroy G.
Nature. 2025 Apr;640(8058):302-304.
doi: 10.1038/d41586-025-01064-5.
PMID: 40200117.
Mitochondria — the supposedly static energy factories that reside inside cells — seem to actually be expert travellers, skipping from one cell to another. This ‘mitochondrial transfer’ has been observed in a wide variety of cells and in organisms as diverse as yeast, molluscs and rodents. Some studies have hinted that cells donate their mitochondria to their neighbours during times of need. Other research suggests that mitochondrial transfer can be a lethal weapon that cancer cells deploy to gain an advantage. But what this means for human health is still a mystery — if it happens inside the human body at all.
How to make great coffee with fewer beans, according to science
Pour-over coffee: Mixing by a water jet impinging on a granular bed with avalanche dynamics.
Ernest Park, Margot Young, Arnold J. T. M. Mathijssen;
Physics of Fluids 1 April 2025; 37 (4): 043332.
https://doi.org/10.1063/5.0257924
Coffee comes with a carbon cost, so using less of it is a good thing — especially if it can be done without giving up your daily dose of life-giving brown elixir. Physicists fine-tuned the ‘pour-over’ method (formerly known, at least in my childhood home, as just ‘making coffee’) to use up to 10% fewer beans. They swapped the coffee grounds for silica gel particles, and the paper filter for a glass cone and lasers, to discover the ideal approach: pour really slowly, and from a great height. This creates “avalanche dynamics”, in which the grains swirl for longer, giving you more coffee bang for your bean buck. How high? “Be reasonable,” says study co-author Arnold Mathijssen. You want to maintain laminar flow, so about 50 centimetres will do it.