MP

Structural basis for the transport and regulation mechanism of the multidrug resistance-associated protein 2. 

Koide E, Pietz HL, Beltran J, Chen J.

Nat Commun. 2025 Jan 8;16(1):484. 

doi: 10.1038/s41467-024-55810-w. 

PMID: 39779684.

Cryo-EM structures of MRP2 in multiple functional states. 

Cryo-EM reveals the structural heterogeneity and conformational flexibility of multidrug efflux pumps MdtB and MdtF.

Surekha Padmanabhan, Clayton Fernando Rencilin, Rupam Biswas, Somnath Dutta.

bioRxiv 2025.04.25.650598; 

doi: https://doi.org/10.1101/2025.04.25.650598.

Cryo-EM structures of MdtB and MdtF. HAE-RND pumps from E.coli.

MdtF = unique class of RND pump (expression is regulated by oxygen availability, crucial for the survival of E.coli in anaerobic conditions).

=> flexible transmembrane domain with significant conformational changes in the core helixes, leading to the closure of the central pore. 

MdtB structure adopts a resting state /MdtF displays structural dynamics in the presence of DDM. 

The apo structures of both pumps unveil novel conformational states of HAE-RND efflux transporters. This structural plasticity may be linked to their oxygen-regulated roles in E. coli.

Structure and transport mechanism of human riboflavin transporters.

Wang K, Chen H, Cheng L, Zhao J, Huang B, Wu D, He X, Zhou Y, Yuan Y, Zhou F, Jiang J, Chen L, Jiang D.

Nat Commun. 2025 May 1;16(1):4078. 

doi: 10.1038/s41467-025-59255-7.

PMID: 40307217.

High-resolution structures of human riboflavin transporters => molecular basis for substrate binding and translocation. The study highlights isoform-specific differences in transport mechanisms among RFVT1-3. Disease-associated mutations cluster around the substrate pathway, affecting function.

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.

The structure of the mitochondrial pyruvate carrier (MPC) shows a functional dimer that forms a hydrophobic channel for pyruvate transport. 

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.

Study showing how various inhibitors bind to the mitochondrial pyruvate carrier, preventing substrate transport. Ligands interact with conserved hydrophobic pockets, disrupting the transport pathway. Molecular simulations suggest an allosteric mechanism of inhibition. These findings support the rational design of MPC-targeting drugs for metabolic intervention.

The non-thermogenic function of opossum UCP1 is independent of its cytoplasmic binding network.

Giorgia Roticiani, Juergen Kreiter, Elena E Pohl.

bioRxiv 2025.04.27.650829; 

doi: https://doi.org/10.1101/2025.04.27.650829.

UCP1 from opossum lacks thermogenic activity: attributed to altered cytosolic salt bridge network. 

=> validity of the proposed mechanism involving these residues in the loss of thermogenic function in opossum UCP1 ?. 

Here: conductance measurements with UCP1, UCP1 mutant, UCP2 or UCP3. 

=> altered cytosolic residues do not explain the lack of thermogenic function in opossum UCP1. Molecular mechanism responsible for the absence of thermogenesis in opossum UCP1 remains unresolved.

Co-development of efflux pump inhibitors with antibiotics on targeting structural and mutational aspects of AcrB subunit.

Chauhan SS, Jamal T, Gupta A, Parthasarathi R.

Mol Divers. 2025 Apr 27. 

doi: 10.1007/s11030-025-11204-8. Online ahead of print.

PMID: 40287901.

Key resistance-linked mutations in AcrB that enhance drug efflux and antibiotic resistance. 

Large-scale virtual screening of natural compounds => discovery of promising AcrB inhibitors. Molecular docking and dynamics show that some inhibitors competitively bind with known antibiotics.

LetA defines a structurally distinct transporter family involved in lipid trafficking.

Cristina C. Santarossa, Yupeng Li, Sara Yousef, Hale S. Hasdemir, Carlos C. Rodriguez, Max B. Haase, Minkyung Baek, Nicolas Coudray, John G. Pavek, Kimber N. Focke, Annika L. Silverberg, Carmelita Bautista, Johannes Yeh, Michael T. Marty, David Baker, Emad Tajkhorshid, Damian C. Ekiert, Gira Bhabha

bioRxiv 2025.03.21.644421; 

doi: https://doi.org/10.1101/2025.03.21.644421.

Structure of E. coli LetAB (=phospholipid transporter essential for outer membrane integrity). 

LetA forms a unique pump-like architecture unrelated to known transporter families and interacts with LetB to create a ~225 Å tunnel for lipid movement. 

New class of membrane transport proteins. 

Using structural, computational, and functional approaches, the authors propose that LetA-like transporters harness proton-motive force to facilitate lipid translocation across the bacterial envelope.

Optimal functioning of the Lpt bridge depends on a ternary complex between the lipocalin YedD and the LptDE translocon.

Gennaris A, Nguyen VS, Thouvenel L, Csoma N, Vertommen D, Iorga BI, Remaut H, Collet JF.

Cell Rep. 2025 Apr 22;44(4):115446. 

doi: 10.1016/j.celrep.2025.115446. Epub 2025 Mar 23.

PMID: 40127101.

Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with Gs.

Felipe Merino, Zoe Koeck, Utz Heinrich Ermel, Philipp Dahlhaus, Anna Grimm, Anja Seybert, Jan Kubicek, Achilleas S Frangakis, Volker Doetsch, Daniel Hilger, and Frank Bernhard.

bioRxiv posted 29 April 2025.

doi:10.1101/2025.04.29.651181.

cell-free system => high-resolution cryo-EM structure of the human β1-adrenergic receptor bound to the Gs protein. The structure captures key interactions between the receptor and G-protein complex, essential for signal transduction. 

This study demonstrates the feasibility of studying full-length GPCRs without detergent solubilization and provides insights into β1AR activation and stabilization mechanisms.

Hidden GPCR structural transitions addressed by multiple walker supervised molecular dynamics (mwSuMD).

Deganutti G, Pipito L, Rujan RM, Weizmann T, Griffin P, Ciancetta A, Moro S, Reynolds CA.

Elife. 2025 Apr 30;13:RP96513. 

doi: 10.7554/eLife.96513.

PMID: 40305095. 

Multiple walker supervised molecular dynamics (mwSuMD) to uncover hidden conformational transitions in GPCRs => rare transitions between active and inactive receptor states not easily captured by standard simulations. It also identifies key intermediate states relevant for ligand efficacy and biased signaling. This computational approach enhances our understanding of GPCR flexibility and function.

Membranes

Teichoic acids in the periplasm and cell envelope of Streptococcus pneumoniae.

Nguyen M, Bauda E, Boyat C, Laguri C, Freton C, Chouquet A, Gallet B, Baudoin M, Wong YS, Grangeasse C, Moriscot C, Durmort C, Zapun A, Morlot C.

Elife. 2025 Apr 23;14:RP105132. 

doi: 10.7554/eLife.105132.

PMID: 40265569.

The study maps the presence and organization of teichoic acids across the periplasm and cell envelope of Streptococcus pneumoniae. 

Cryo-EM + biochemical analyses => authors show that these polymers bridge the cytoplasmic membrane and cell wall. Teichoic acids contribute to envelope integrity and antibiotic resistance. These findings challenge traditional models of Gram-positive cell envelope architecture.

Long-term memory in lipid assemblies: Rate-independent hysteresis in the ripple-to-liquid-disordered transition of sphingomyelin bilayers. 

Llombart P, Arada I, González-Ramírez EJ, Alonso A, MacDowell LG, Goñi FM.

J Chem Phys. 2025 Apr 7;162(13):135101. 

doi: 10.1063/5.0252051. 

PMID: 40167004.

Sphingomyelin bilayers exhibit rate-independent hysteresis during the ripple-to-liquid disordered phase transition. The system retains a memory of its previous thermodynamic state, indicative of long-term structural organization. Such memory effects are unusual in lipid bilayers and could impact MP function.

Comprehensive Insights into the Cholesterol-Mediated Modulation of Membrane Function through Molecular Dynamics Simulations.

Khodadadi E, Khodadadi E, Chaturvedi P, Moradi M.

ArXiv [Preprint]. 2025 Apr 7:arXiv:2504.05564v1.

PMID: 40297234.

MD => study shows how cholesterol modulates membrane properties at the molecular level. Cholesterol increases membrane order, reduces permeability, and affects lipid-protein interactions. The simulations also reveal how cholesterol’s location and orientation influence local bilayer behavior.

Protonation-Regulated Membrane-Insertion Dynamics of pH Low-Insertion Peptide: Metastable Molecular Conformations and Their Transitions.

Qiu J, Ma D, You X, Jia Q, Hu S, Xu C, Cao B, Yang K, Han W, Lu Y, Yuan B, Li M.

ACS Nano. 2025 Apr 29;19(16):15685-15697. 

doi: 10.1021/acsnano.4c18301. Epub 2025 Apr 18.

PMID: 40247709.

This study tracks the membrane insertion dynamics of pH Low-Insertion Peptides (pHLIP) as a function of protonation state. The authors identify metastable conformations and transition paths between membrane-bound and inserted states. The data suggest that pH-driven conformational change underlies selective insertion.

Curvature-sensing and generation by membrane proteins: a review.

Noguchi H.

Soft Matter. 2025 Apr 30. doi: 10.1039/d5sm00101c. Online ahead of print.

PMID: 40302616. 

Engineering cardiolipin binding to an artificial membrane protein reveals determinants for lipid-mediated stabilization.

Abramsson ML, Corey RA, Skerle JL, Persson LJ, Anden O, Oluwole AO, Howard RJ, Lindahl E, Robinson CV, Strisovsky K, Marklund EG, Drew D, Stansfeld PJ, Landreh M.

Elife. 2025 Apr 30;14:RP104237. 

doi: 10.7554/eLife.104237.

PMID: 40304703. 

Engineered binding sites on an artificial MP used to study CL interactions and their effect on protein stability. Structural and biochemical analyses show that specific residues and binding modes enhance stabilization. The findings point to key determinants of lipid-protein interactions that maintain protein conformation.

Molecules

Examining the Thermotropic properties of Large, Circularized Nanodiscs.

Arcario MJ, Dalal V, Fan D, Cheng WWL.

bioRxiv [Preprint]. 2025 Apr 10:2025.04.07.647641. 

doi: 10.1101/2025.04.07.647641.

PMID: 40291733.

Large circularized NDs characterized here to assess their thermotropic behavior and suitability for MP studies. The discs show clear lipid phase transitions and stability across temperature ranges. Large diameter => they are suitable for multimeric or large membrane complexes. These findings support the utility of circularized nanodiscs in biophysical research.

Evaluation of Membrane Mimetics for the Native Ion Mobility─Mass Spectrometry Analysis of Membrane Proteins.

Levesque I, Parson KF, Fantin SM, Ruotolo BT.

Anal Chem. 2025 Apr 29. 

doi: 10.1021/acs.analchem.4c06629. Online ahead of print.

PMID: 40301699.

This study evaluates various membrane mimetics for preserving native conformations of MPs in ion mobility–mass spectrometry. Amphipols, SMALPs, and nanodiscs were tested for stability and structural integrity of protein complexes. Some mimetics preserve native topology better than detergents.

Methods

In Situ Light-driven pH Modulation for NMR Studies. 

Barde A, Han R, Olson MA, Tonelli M, Rienstra CM, Henzler-Wildman KA, Ravula T.

Angew Chem Int Ed Engl. 2025 Mar 22:e202501440. 

doi: 10.1002/anie.202501440. Epub ahead of print. 

PMID: 40120101.

NMR +++ for protonation events with site-specific resolution (e.g manual titration of sample pHat different pH values) but requires extensive sample handling. 

Here: novel approach to control pH in NMR samples upon in situ photo illumination => precise, calibrated, and noninvasive change of sample pH within an NMR magnet, dramatically reducing the necessary sample handling.

A universal cannabinoid CB1 and CB2 receptor TR-FRET kinetic ligand-binding assay.

Borrega-Roman L, Hoare BL, Kosar M, Sarott RC, Patej KJ, Bouma J, Scott-Dennis M, Koers EJ, Gazzi T, Mach L, Barrondo S, Sallés J, Guba W, Kusznir E, Nazaré M, Rufer AC, Grether U, Heitman LH, Carreira EM, Sykes DA, Veprintsev DB.

Front Pharmacol. 2025 Apr 9;16:1469986. 

doi: 10.3389/fphar.2025.1469986. eCollection 2025.

PMID: 40271066. 

Cation-controlled assembly, activity, and organisation of biomimetic DNA receptors in synthetic cell membranes.

Elita Peters, Diana A. Tanase, Lorenzo Di Michele, Roger Rubio-Sánchez.

bioRxiv 2025.04.27.650532; 

doi: https://doi.org/10.1101/2025.04.27.650532.

Nickel-NTA lipid-monolayer affinity grids allow for high-resolution structure determination by cryo-EM.

Aleksandra Skrajna, Emily Robinson, Kevin Cannon, Reta Sarsam, Richard G. Ouellette, Patrick Brennwald, Robert K. McGinty, Joshua D. Strauss, Richard W. Baker.

bioRxiv 2025.04.24.650495; 

doi: https://doi.org/10.1101/2025.04.24.650495.

Affinity grids = promising tools in EM grid-preparation (selective concentration of proteins + protecting samples from the air-water interface). 

Here: Ni-NTA lipid monolayers as tool for high-resolution single particle cryo-EM. First affinity grids = holey carbon layer coated with Ni-NTA lipid = complicated protocols (conducted before the “resolution revolution”).

TmDet 4.0: determining membrane orientation of transmembrane proteins from 3D structure.

Tusnády GE, Gerdán C.

Nucleic Acids Res. 2025 Apr 25:gkaf338. 

doi: 10.1093/nar/gkaf338. Online ahead of print.

PMID: 40276976.

Miscellaneous

Structural basis of human Mediator recruitment by the phosphorylated transcription factor Elk-1.

Monté D, Lens Z, Dewitte F, Fislage M, Aumercier M, Verger A, Villeret V. Nat Commun. 2025 Apr 22;16(1):3772. 

doi: 10.1038/s41467-025-59014-8. 

PMID: 40263353. 

Structural mechanism by which the phosphorylated transcription factor Elk-1 recruits the human Mediator complex. Using X-ray crystallography and biochemical assays, the authors show how phosphorylated Elk-1 binds specifically to the Med23 subunit via a defined interaction motif. This interaction is essential for Elk-1–mediated gene activation downstream of MAPK signaling. The findings clarify how transcriptional specificity is achieved through dynamic protein–protein interactions during signal-induced gene expression.

COVID-19 in Space: Possible Health Risks and Preparedness Guidelines.

Ishan Vashishat, Sanghyun Eddie Han, Barnabe D. Assogba

bioRxiv 2025.04.23.650113; 

doi: https://doi.org/10.1101/2025.04.23.650113.

Preprint exploring the potential health risks of COVID-19 transmission and progression in spaceflight environments. It discusses how microgravity, altered immune function, and closed-loop habitats could exacerbate viral persistence and transmission among astronauts.

The temperature dependence of binding entropy is a selective pressure in protein evolution.

Rosemary Georgelin, Hannah Bott, Joe Kaczmarski, Rebecca Frkic, Li Lynn Tan, Nobuhiko Tokuriki, Matthew A Spence, Colin Jackson

bioRxiv 2025.03.23.644840; 

doi: https://doi.org/10.1101/2025.03.23.644840.

This study investigates how the temperature sensitivity of binding entropy influences protein evolution. Using experimental and computational data, the authors show that proteins adapted to different thermal environments exhibit distinct entropic responses during ligand binding. These differences affect binding affinity and stability, implying that entropy modulation is a target of natural selection. The findings suggest that temperature-dependent binding entropy plays an active evolutionary role in shaping protein-ligand interactions.

How metal singers scream without pain

https://www.sciencefriday.com/articles/death-metal-singers-vocal-research/?utm_source=Live+Audience&utm_campaign=5292d6ca38-nature-briefing-daily-20250430&utm_medium=email&utm_term=0_b27a691814-5292d6ca38-50537092

Scientists and death-metal musicians — funded by science fans online — are joining forces to investigate how the singers push their voices to the limit without injuring their vocal chords. “When you are starting to look into the back of the throat and doing these different procedures, you’re just struck automatically with how different each one of [these artists] maneuvers their larynx or their vocal tract,” says voice scientist Amanda Stark. “There’s just these eye-opening big moments of, like, holy cow, there’s so much uniqueness here on how people can achieve sounds.”