MP
The structure of human sweetness.
Zhang Juen, Zhengyuan Lu, Ruihuan Yu, Andrew N. Chang, Brian Wang, Anthony W.P. Fitzpatrick, Charles S. Zuker.
Cell, May 07, 2025 Open access.
doi: 10.1016/j.cell.2025.04.021.
Cryo-EM structure of the human sweet taste receptor TAS1R2/TAS1R3.
Authors show how various sweet molecules bind at multiple sites within the receptor. Allosteric coupling between the two subunits => receptor’s broad sensitivity and nuanced signaling.
Gating mechanism of the two-pore-domain potassium channel THIK1.
Fang X, Jin H, Wang J, Zhang R, Li B.
Nat Struct Mol Biol. 2025 Apr 30.
doi: 10.1038/s41594-025-01542-4. Online ahead of print.
PMID: 40307591.
Structural basis for gating in THIK1, a two-pore-domain (K2P) potassium channel. Gating involves tilting motions of TM helices and is influenced by lipid interactions. THIK1 displays non-canonical responses to membrane tension, differentiating it from other K2P channels.
Cryo-EM of Mitochondrial Complex I and ATP Synthase.
Kühlbrandt W, Carreira LAM, Yildiz Ö.
Annu Rev Biophys. 2025 May;54(1):209-226.
doi: 10.1146/annurev-biophys-060724-110838.
PMID: 40327437.
Review summarizing recent cryo-EM studies of mitochondrial Complex I and ATP synthase.Emphasis is placed on conformational coupling, proton translocation, and assembly intermediates.
A Novel Model for Proton Transport Mediated by Uncoupling Protein 1.
Luise Jacobsen, Sneha Menon, Michael James Gaudry, Ali Asghar Hakami Zanjani, Peter Reinholdt, Martin Jastroch, and Himanshu Khandelia.
bioRxiv posted 1 May 2025.
doi:10.1101/2025.04.28.650983.
New model for how UCP1 mediates proton transport in mitochondria.
MD => FA may enable dynamic gating of proton conduction pathways in UCP1. The model proposes cooperative behavior among multiple binding sites, deviating from classical proton shuttle concepts.
Functional conformations or poor mimetics?
Nury H, Efremov RG.
Structure. 2025 May 1;33(5):840-842.
doi: 10.1016/j.str.2025.04.002.
PMID: 40315820.
Interesting editorial on Hoffmann et al. Structure. 2025 Feb 28. (PMID: 40056915), see 20250417_membrane digest ;-D): importance of functional validation in structural biology. Authors advocate for combining cryo-EM with dynamic or activity-based assays to discriminate real functional states from artifacts.
The versatile role of YidC in membrane protein biosynthesis and quality control.
Caliseki M, Schaffitzel C, Kabasakal BV.
Biochim Biophys Acta Mol Cell Res. 2025 Jun;1872(5):119956.
doi: 10.1016/j.bbamcr.2025.119956. Epub 2025 Apr 10.
PMID: 40221051.
YidC = conserved membrane insertase that supports protein insertion, folding, and quality control in membranes.
Here: review outlining its dual role as a chaperone and insertase, including its cooperation with the SecYEG translocon and ribosomes + YidC’s involvement in degrading misfolded proteins and maintaining membrane proteostasis.
Revealing the location and dynamics of a concealed binding site in the dopamine transporter.
Zhu R, Sandtner W, Stockner T, Heilinger A, Holy M, Kudlacek O, Wildling L, Saha K, Fröhlich AS, Bindl M, Tziortzouda P, Haider A, Gobl J, Suh SH, Khan JA, Bicher J, Kastner N, Ebner A, Gruber HJ, Freissmuth M, Newman AH, Sitte HH, Hinterdorfer P.
Nat Commun. 2025 May 6;16(1):4197.
doi: 10.1038/s41467-025-59511-w.
PMID: 40328781.
Sm-force spectroscopy + mutagenesis + structural modeling => identification of a previously hidden binding site in the dopamine transporter.
The site undergoes conformational transitions critical for substrate translocation and binding at this site modulates transporter dynamics and inhibitor sensitivity.
A lipoprotein partner for the Escherichia coli outer membrane protein TolC.
Jim Horne, Elise Kaplan, Ben HS Jin, Emmanouela Petsolari, Jan M. Gradon, Yvette Ntsogo, Andrzej Harris, Dingquan Yu, Ben F. Luisi
bioRxiv 2025.03.19.644130;
doi: https://doi.org/10.1101/2025.03.19.644130.
Novel lipoprotein identified !
It interacts with TolC in E. coli. Using cryo-EM, cross-linking, and modeling, authors map the interaction interface and propose a mechanism for how it may modulate TolC gating.
=> additional regulatory layer in efflux function, potentially influencing antibiotic resistance ?
Conduction pathway for potassium through the E. coli pump KdpFABC.
Adel Hussein, Xihui Zhang, Bjørn P. Pedersen, and David L Stokes.
bioRxiv posted 6 May 2025
doi:10.1101/2025.05.05.652293.
Cryo-EM and functional assays to describe the K⁺ conduction pathway in the high-affinity KdpFABC pump of E. coli.
=> identification of a hydrated cavity and a dynamic gating mechanism that supports active potassium uptake. The structural transitions suggest an electrogenic pumping mechanism driven by ATP hydrolysis.
Membranes
A Minimalist Model Lipid System Mimicking the Biophysical Properties of Escherichia coli’s Inner Membrane.
Tormena N, Pilizota T, Voïtchovsky K.
Langmuir. 2025 May 7.
doi: 10.1021/acs.langmuir.5c01138. Online ahead of print.
PMID: 40335890.
Simplified artificial lipid system that mimics the fluidity and asymmetry of the E. coli IM. Model uses tailored lipid mixtures to recreate native-like membrane packing and elasticity.
Compositional versatility enables biologically inspired reverse micelles for study of protein-membrane interactions.
Walters SH, Signorelli RL, Payne AG, Hojjatian A, Fuglestad B.
Soft Matter. 2025 May 7;21(18):3547-3557.
doi: 10.1039/d5sm00033e.
PMID: 40208197.
Design of tunable reverse micelles that mimic the complexity of cellular membranes for protein interaction studies.
Compositional flexibility in micelle formation allows precise modulation of curvature, polarity, and lipid composition. These reverse micelles facilitate reconstitution of MPs in confined, biologically relevant environments.
ATP-release pannexin channels are gated by lysophospholipids.
Henze E, Burkhardt RN, Fox BW, Schwertfeger TJ, Gelsleichter E, Michalski K, Kramer L, Lenfest M, Boesch JM, Lin H, Schroeder FC, Kawate T.
Elife. 2025 May 1;14:RP107067.
doi: 10.7554/eLife.107067.
PMID: 40309905.
Study showing that pannexin channels, responsible for ATP release in various physiological processes, are modulated by lysophospholipids.
Electrophysiology, lipidomics, and structural approaches => lysophosphatidylserine and related lipids open pannexin channels via specific lipid-protein interactions: a novel lipid-based gating mechanism.
Dynamic Shape Modulation of Deflated and Adhered Lipid Vesicles.
Gianna C Wolfisberg, Jaime Agudo-Canalejo, Pablo C Bittmann, Eric R Dufresne, Robert W Style, and Aleksander A Rebane.
bioRxiv posted 7 May 2025.
doi:10.1101/2025.05.06.650387.
Study showing how lipid vesicles adhering to surfaces undergo shape changes under deflation.
Time-lapse imaging and mechanical modeling => adhesion and osmotic stress induce dramatic morphological transitions, including tubulation and vesicle collapse. Observed behaviors are governed by membrane tension, curvature, and substrate interactions.
Membrane asymmetry facilitates murine norovirus entry and persistent enteric infection.
Stewart BM, Pierce LR, Olson MC, Ji C, Orchard RC.
PLoS Biol. 2025 Apr 17;23(4):e3003147.
doi: 10.1371/journal.pbio.3003147. eCollection 2025 Apr.
PMID: 40245088.
Lipid asymmetry in host cell membranes plays a crucial role in murine norovirus entry and infection persistence.
Lipidomics, microscopy, and infection assays => authors show that disruption of membrane asymmetry impairs viral binding and internalization. This asymmetry promotes a lipid environment favorable to viral fusion and genome release.
= important host factor in enteric viral infection and suggests potential antiviral targets.
Supported Lipid Bilayer Arrays Formed from Inkjet-Printed Lipid Spots.
Tanimoto Y, Yamada M, Fujii M, Kitayama K, Hayashi F, Hosokawa C, Morigaki K.
Langmuir. 2025 May 5.
doi: 10.1021/acs.langmuir.4c04033. Online ahead of print.
PMID: 40323044.
Novel method for forming SLB arrays using inkjet printing of lipid droplets !
=> precise, high-throughput patterning of SLBs on solid supports with control over lipid composition. Arrays retain fluidity and support protein incorporation: suitable for biosensing and membrane-protein studies.
ArchLips: A comprehensive in silico database for high-throughput identification of archaeal lipids.
Fengfeng Zheng, Wenyong Yao, Wei He, Wan Zhang, Yufei Chen, Huahui Chen, Zhirui Zeng, Xiao-Lei Liu, Su Ding, Yanhong Zheng, Linan Huang, Yuanqing Zhu, and Chuanlun Zhang.
bioRxiv posted 6 May 2025.
doi:10.1101/2025.05.05.652033.
ArchLips = computational database designed for identifying archaeal lipids from MS data. It integrates structural prediction, lipid fragmentation profiles, and lipid biosynthesis pathways to facilitate lipid annotation.
Molecules
Assembly of Detergents with Highly Branched Dicarboxylate Clamps for Membrane Protein Studies.
Nguyen KA, Falson P, Boumendjel A.
ChemistryOpen. 2025 May 6:e2500122.
doi: 10.1002/open.202500122. Online ahead of print.
PMID: 40326160.
New class of detergents featuring branched dicarboxylate clamps designed for membrane protein stabilization.
These detergents improve solubilization efficiency and structural integrity of various MPs. Superior preservation of protein function and homogeneity compared to conventional detergents.
Methods
Analyzing the distribution of cell membrane receptors in real-time based on multiple molecule force spectroscopy.
Chen B, Li S, Zhang J, Li X, Zhang Z, Song X, Shan Y.
Talanta. 2025 Apr 30;294:128242.
doi: 10.1016/j.talanta.2025.128242. Online ahead of print.
PMID: 40318488.
Real-time method for mapping cell membrane receptors using multiple molecule force spectroscopy.
Enables nanoscale resolution of receptor distribution and binding dynamics under physiological conditions. Detects receptor-ligand interactions with high sensitivity and temporal precision.
Advancing time-resolved structural biology: latest strategies in cryo-EM and X-ray crystallography.
Banari A, Samanta AK, Munke A, Laugks T, Bajt S, Grünewald K, Marlovits TC, Küpper J, Maia FRNC, Chapman HN, Oberthür D, Seuring C.
Nat Methods. 2025 May 1.
doi: 10.1038/s41592-025-02659-6. Epub ahead of print.
PMID: 40312512.
Recent advances in time-resolved cryo-EM and time-resolved X-ray crystallography techniques (visualization of structural transitions at millisecond to femtosecond scales). Authors discuss innovations in sample delivery, triggering mechanisms, and ultrafast data acquisition for capturing dynamic molecular events.
AF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2.
Matteo Cagiada, F. Emil Thomasen, Sergey Ovchinnikov, Charlotte M. Deane, Kresten Lindorff-Larsen.
bioRxiv 2025.04.16.649219;
doi: https://doi.org/10.1101/2025.04.16.649219.
AF2χ = new tool that enhances AlphaFold2 predictions by generating side-chain rotamer distributions instead of single static conformations.
A Dynamic Sugar-Selective Bacterial Nanopore for Targeted Antibiotic Transport.
Sk S, Majumdar BB, Vikraman D, Mahanta K, Soman A, Rajavelu A, Mondal J, Mahendran KR.
Small. 2025 May 6:e2502110.
doi: 10.1002/smll.202502110. Online ahead of print.
PMID: 40326190.
Synthetic nanopore engineered to selectively recognize and transport sugar-modified antibiotics.
MD and electrophysiology => the pore adapts dynamically to specific sugar moieties, allowing selective passage: enhances antibiotic delivery while reducing off-target effects.
Generation of shark Single-Domain antibodies as an aid for Cryo-EM structure determination of membrane Proteins: Use hyaluronan synthase as an example.
Penghui Deng, Xiaoyue Zhang, Jianqing Wen, Mingce Xu, Pengwei Li, Hao Wang, Yunchen Bi.
Journal of Structural Biology: X, 2025, 100126, ISSN 2590-1524,
https://doi.org/10.1016/j.yjsbx.2025.100126.
(https://www.sciencedirect.com/science/article/pii/S2590152425000078)
Authors describe a platform to generate shark-derived VNARs (single-domain antibodies) targeting MPs. They optimize conditions for antigen stability, VNAR expression, and immunization to yield a high-affinity clone.
Cryo-EM reveals a unique binding epitope, distinct from camelid VHHs.
First structure of a MP–VNAR complex.
Microbio
Synergistic pathogenesis: exploring biofilms, efflux pumps and secretion systems in Acinetobacter baumannii and Staphylococcus aureus.
Bell I PJ, Muniyan R.
Arch Microbiol. 2025 May 2;207(6):134.
doi: 10.1007/s00203-025-04336-w.
PMID: 40314822.
This review discussing how A. baumannii and S. aureus leverage biofilms, efflux pumps, and secretion systems in coordinated pathogenesis.
Pseudomonas aeruginosa clinical isolates can encode plastic-degrading enzymes that allow survival on plastic and augment biofilm formation.
Sophie A. Howard, Rubén de Dios, Evgenia Maslova, Antonis Myridakis, Thomas H. Miller, Ronan R. McCarthy.
Cell Reports, Volume 0, Issue 0, 115650.
doi: 10.1016/j.celrep.2025.115650.
P. aeruginosa isolates can produce enzymes that degrade plastic polymers 😱.
Plastic degradation => survival in hospital environments and enhancement of biofilm formation on synthetic surfaces.
Genomic and biochemical analyses reveal plasticase gene clusters and their regulation.
Miscellaneous
Importance of diversity and representation in science: benefits towards strengthening our response to global challenges.
Perez-Sepulveda BM, Cunningham-Oakes E, Waters EV.
NPJ Antimicrob Resist. 2025 Apr 11;3(1):26.
doi: 10.1038/s44259-025-00101-7.
PMID: 40216948.
Critical role of diversity and inclusion in advancing scientific innovation: diverse teams foster creativity, resilience, and broader impact, particularly in global health and antimicrobial resistance.
Authors support structural changes to enhance equity in research environments. The article calls for global efforts to integrate representation into scientific leadership and collaboration.
Blood of man who’s had 200 snake bites helps make a potent antivenom.
Bourzac K.
Nature. 2025 May 2.
doi: 10.1038/d41586-025-01325-3. Epub ahead of print.
PMID: 40316850.
The blood of a snake fancier who has been bitten by venomous snakes hundreds of times has been used to develop a potent antivenom. The therapy protects mice against the venoms of 19 species of dangerous snake, including the deadly king cobra (Ophiophagus hannah). The research could lead to direly needed treatments, scientists say. However, its reliance on material from a person who performed dangerous experiments on himself makes it ethically murky. “We did not advise Friede to do this and no one else needs to do this again,” says co-author Jacob Glanville, chief executive of biomedical firm Centivax.
The SIK3-N783Y mutation is associated with the human natural short sleep trait.
Chen H, Xing Y, Wan C, Zhang Z, Shi Z, Liang Y, Jin C, Chen Y, Zhou X, Xu J, Ptáček LJ, Fu YH, Shi G.
Proc Natl Acad Sci U S A. 2025 May 13;122(19):e2500356122.
doi: 10.1073/pnas.2500356122. Epub 2025 May 5.
PMID: 40324078.
From Thomas Edison to Benjamin Franklin, history is speckled with luminaries claimed to be able to thrive on as little as three hours of sleep. Now scientists have identified genetic mutations that probably contributes to some people’s limited sleep needs. One mutation, when genetically engineered into mice, caused the animals to sleep half an hour per day less than their unmodified brethren.
Genetic and training adaptations in the Haenyeo divers of Jeju, Korea.
Aguilar-Gómez D, Bejder J, Graae J, Ko Y, Vaughn A, Clement K, Tristani-Firouzi M, Lee JY, Nordsborg NB, Nielsen R, Ilardo M.
Cell Rep. 2025 Apr 16:115577.
doi: 10.1016/j.celrep.2025.115577. Epub ahead of print.
PMID: 40318638.
This paper investigates genetic and physiological traits of the Haenyeo, traditional female free-divers from Jeju Island. Genomic analysis reveals variants linked to low blood pressure, cold tolerance, and red blood cell regulation. These adaptations appear widespread among island residents, not only active divers. The study illustrates human evolution under cultural and environmental pressures.
Historic pandemic treaty is a triumph in a world being torn apart.
Nature. 2025 May;641(8061):8.
doi: 10.1038/d41586-025-01307-5.
PMID: 40301615.
Editorial celebrating the ratification of a global pandemic preparedness treaty (”a rare diplomatic success in divisive times”). The treaty mandates surveillance, equitable vaccine access, and transparency. It reflects lessons from COVID-19 and aims to prevent future public health failures.
Bacteria encode post-mortem protein catabolism that enables altruistic nutrient recycling.
Gibson SER, Frost I, Hierons SJ, Moses T, Poon WCK, West SA, Cann MJ.
Nat Commun. 2025 Feb 13;16(1):1400.
doi: 10.1038/s41467-025-56761-6.
PMID: 39948360.
Certain bacteria express genes for breaking down dead sibling cells, releasing nutrients for the living community: altruistic post-mortem catabolism that promotes population resilience in nutrient-poor environments. Genetic and biochemical data show regulated activation upon cell death cues.
And the winner of this year’s ‘Dance Your Ph.D.’ contest is …
Science 1 May 2025
Helsinki chemist’s food-themed frolic wins overall honors as other awards recognize physics laser raps, swaying leaf cells, and collective dancing takeovers.