MP
Surface lipoprotein sorting by crosstalk between Lpt and Lol pathways in gram-negative bacteria.
Luo Q, Wang C, Qiao S, Yu S, Chen L, Kim S, Wang K, Zheng J, Zhang Y, Wu F, Lei X, Lou J, Hennig M, Im W, Miao L, Zhou M, Bei W, Huang Y.
Nat Commun. 2025 May 10;16(1):4357.
doi: 10.1038/s41467-025-59660-y.
PMID: 40348743.
Identification of a crosstalk between the Lpt and Lol pathways.
Cryo-EM structures + in vitro reconstitution => LptDE can act as a surface lipoprotein translocon, coordinating with LolCDE to traffic lipoproteins directly to the bacterial surface.
This crosstalk explains how surface-exposed lipoproteins bypass typical periplasmic transit.
Allosteric modulation of SERCA pumps in health and disease: structural dynamics, posttranslational modifications, and therapeutic potential.
Viskupicova J, Michel Espinoza-Fonseca L.
J Mol Biol. 2025 May 9:169200. doi: 10.1016/j.jmb.2025.169200. Online ahead of print.
PMID: 40349954.
Review discussing how allosteric regulation, posttranslational modifications, and interacting molecules control SERCA pump dynamics (recent structural and computational studies <=> physiological function and disease).
Allosteric targeting = promising therapeutic strategy (cardiac and skeletal muscle disorders).
Proximity-induced membrane protein degradation for cancer therapies.
Zhang D, Wang Z, Inuzuka H, Wei W.
RSC Med Chem. 2025 May 2.
doi: 10.1039/d5md00141b. Online ahead of print.
PMID: 40365034.
Novel strategy for selectively degrading MPs in cancer cells using proximity-induced degrader molecules. These agents tether E3 ligases to TM targets, triggering proteasomal degradation without genetic manipulation.
=> promise against hard-to-drug cancer-associated proteins.
Ist2 promotes lipid transfer by Osh6 via its membrane tethering and lipid scramblase activities.
Alicia Fabbre, Camille Syska, Heitor Gobbi Sebinelli, Anna Cardinal, Maud Magdeleine, Noha Al-Qatabi, Juan Martín D Ambrosio, Cédric Montigny, Guillaume Lenoir, Alenka Copic, and Guillaume Drin.
bioRxiv posted 10 May 2025
doi:10.1101/2025.05.06.652365.
Ist2 (multi-domain MP), facilitates lipid transfer by tethering membranes and enhancing lipid scrambling. Authors show that Ist2 boosts Osh6-mediated PS transfer through physical proximity and bilayer remodeling.
Reconstitution experiments confirm dual activities (scramblase and tether) that cooperatively accelerate lipid exchange.
Mechanistic insights into Enterocin C targeting the undecaprenyl phosphate recycling protein BacA.
Victor Folcher, Rodolphe Auger, Clara Louche, Pascale Serror, and Thierry Touze.
bioRxiv posted 12 May 2025.
doi:10.1101/2025.05.12.652377.
Study exploring how the antimicrobial peptide Enterocin C inhibits BacA, a key enzyme involved in recycling undecaprenyl phosphate, essential for bacterial cell wall biosynthesis.
Biochemical assays and mutational analysis => identification of critical residues in BacA that mediate peptide binding and inhibition.
Structural modeling => Enterocin C may disrupt lipid carrier cycling, weakening PG synthesis.
Targeting the selectivity filter to drastically alter the activity and substrate spectrum of a promiscuous metal transporter.
Yuhan Jiang, Michael Nikolovski, Tianqi Wang, Keith MacRenaris, Thomas V. O’Halloran, and Jian Hu.
bioRxiv posted 13 May 2025
doi:10.1101/2025.05.07.652779.
Engineering of a metal transporter by modifying its selectivity filter to reshape ion specificity and activity.
Precise mutations switch the transporter’s preference across different divalent metals (checked by structural and functional analyses).
Membranes
Lipid-degrading small molecule kills cancer cells by ferroptosis.
Lange M, Olzmann JA.
Nature. 2025 May 7.
doi: 10.1038/d41586-025-01337-z. Epub ahead of print.
PMID: 40335796.
New molecule that induces ferroptosis in cancer cells by degrading membrane lipids. The compound triggers iron-dependent oxidative lipid damage, selectively targeting tumor cells with heightened lipid vulnerability.
=> promising strategy to exploit metabolic weaknesses in aggressive cancers.
Caveolin assemblies displace one bilayer leaflet to organize and bend membranes.
Doktorova M, Daum S, Reagle TR, Cannon HI, Ebenhan J, Neudorf S, Han B, Sharma S, Kasson P, Levental KR, Bacia K, Kenworthy AK, Levental I.
Proc Natl Acad Sci U S A. 2025 May 20;122(20):e2417024122.
doi: 10.1073/pnas.2417024122. Epub 2025 May 13.
PMID: 40359049.
Study explaining how caveolae are shaped and stabilized.
Cryo-EM and simulations => caveolins form oligomeric scaffolds that wedge into one leaflet of the bilayer, inducing curvature and asymmetry. The inserted domain causes membrane bending by displacing lipids asymmetrically, unlike typical bilayer-bending mechanisms.
Cyclization of archaeal membrane lipids impacts membrane protein activity and archaellum formation.
Yang W, Feng X, Chen H, Liman GLS, Santangelo TJ, Zhang C, Zeng Z.
Proc Natl Acad Sci U S A. 2025 May 20;122(20):e2423648122.
doi: 10.1073/pnas.2423648122. Epub 2025 May 12.
PMID: 40354536.
Cyclopentane ring formation in archaeal membrane lipids regulates the fluidity and function of the membrane => impact on the activity of embedded MPs and the assembly of the archaellum, a motility apparatus.
Engineering curvature: block copolymer lithography for the fabrication of curved lipid membranes and their impact on protein-membrane interactions.
Suarez Menendez L, Owen DJ, Zaccai NR, Maestro A, Alvarez-Fernandez A.
J Mater Chem B. 2025 May 8.
doi: 10.1039/d5tb00689a. Online ahead of print.
PMID: 40337829.
Block copolymer lithography to create curved substrates that mimic the geometry of cellular membranes. These engineered surfaces allow controlled investigation of how membrane curvature influences protein binding and dynamics.
Snapshots of mitochondrial fission imaged by cryo-scanning transmission electron tomography.
Kirchweger P, Wolf SG, Varsano N, Dadosh T, Resch GP, Elbaum M.
J Cell Sci. 2025 May 1;138(9):jcs263639.
doi: 10.1242/jcs.263639. Epub 2025 May 14.
PMID: 40365741.
Mitochondrial fission in action using high-resolution cryo-STET imaging: constriction sites and remodeling of OM and IM during division.
Asymmetric phase transitions in lipid bilayers: coupling or bending?
Krompers M, Jaki M, Götz S, Lembeck J, Kaul L, Holzer M, Heerklotz H.
Faraday Discuss. 2025 May 6.
doi: 10.1039/d5fd00003c. Epub ahead of print.
PMID: 40326851.
The study investigating how asymmetric lipid composition affects phase transitions in bilayers (experiments + modeling).
Leaflet asymmetry => mechanical bending or not if interleaflet coupling.
Protein-induced membrane asymmetry modulates OMP folding kinetics and stability.
Machin JM, Ranson NA, Radford SE.
Faraday Discuss. 2025 May 8.
doi: 10.1039/d4fd00180j. Online ahead of print.
PMID: 40338084.
Membrane asymmetry influences the folding and stability of OMPs.
Single-molecule kinetics and model membranes => asymmetric bilayers accelerate or hinder OMP folding depending on leaflet composition.
Role of lipid environment in controlling membrane protein assembly.
Bioinspired Design Rules for Flipping across the Lipid Bilayer from Systematic Simulations of Membrane Protein Segments.
ByungUk Park and Reid C Van Lehn.
First published on 09 May 2025.
Mol. Syst. Des. Eng., 2025, Accepted Manuscript.
https://doi.org/10.1039/D5ME00032G.
MD to identify sequence motifs and structural features that promote spontaneous flipping of MP segments.
Deciphering the language of mingling lipids and proteins.
Overduin M, Bhat R, Dieudonné T, Zhang P, Kervin TA.
Curr Opin Struct Biol. 2025 May 7;92:103061.
doi: 10.1016/j.sbi.2025.103061. Epub ahead of print.
PMID: 40339327.
Review outlining how lipids and proteins communicate to shape membranes. The authors categorize membrane regions based on lipid-protein composition and properties like curvature and domain formation.
Lipid “grammar” and phase-driven behavior are discussed: proposition of frameworks to interpret lipid-protein code in membrane signaling and function.
Molecules
Recent Advances in Detergent Chemistry and Handling Support Membrane Protein Analysis Including Lipid Interactions.
Alker K, Behnke JS, Urner LH.
Chemistry. 2025 May 13:e202501549.
doi: 10.1002/chem.202501549. Online ahead of print.
PMID: 40357652.
Review on recent progress in detergent formulations and strategies for solubilizing MPs while preserving lipid interactions: polymer-based surfactants, cleavable detergents, and phase-optimized systems.
Salipro technology in membrane protein research.
Mostafavi S, Custódio TF, Jungnickel KEJ, Löw C.
Curr Opin Struct Biol. 2025 May 10;93:103050. doi: 10.1016/j.sbi.2025.103050. Online ahead of print.
PMID: 40349676.
The review on applications (pharmacology, cryo-EM, and drug screening) of the Salipro technology = versatile platform for stabilizing MPs in lipid-like environments using ND-like assemblies.
=> enhances protein solubility, structural integrity, and activity in biochemical and structural assays.
Methods
Designer artificial environments for membrane protein synthesis.
Meyer C, Arizzi A, Henson T, Aviran S, Longo ML, Wang A, Tan C.
Nat Commun. 2025 May 10;16(1):4363. doi: 10.1038/s41467-025-59471-1.
PMID: 40348791.
Synthetic, cell-free systems tailored to support the folding and insertion of MPs. By engineering lipid compositions, energy supplies, and scaffold proteins, the authors optimize in vitro translation conditions.
TS2CG as a membrane builder.
Fabian Schuhmann, Jan A Stevens, Neda Rahmani, Isabell Lindahl, Chelsea May Brown, Christopher Brasnett, Dimitrios Anastasiou, Adrià Bravo Vidal, Beatrice J. Geiger, Siewert-Jan Marrink, and Weria Pezeshkian.
bioRxiv posted 9 May 2025.
doi:10.1101/2025.04.16.649160.
TS2CG = new computational framework to build CG membrane models from atomistic data. TS2CG automates the translation of lipid and protein systems into Martini-compatible CG representations.
gorder: Comprehensive tool for calculating lipid orderparameters from molecular simulations.
Ladislav Bartos, Peter Pajtinka, and Robert Vácha.
bioRxiv posted 8 May 2025 doi:10.1101/2025.05.07.652627.
gorder = software package designed to compute various lipid order parameters directly from MD.
Accommodates multiple FFs and simulation outputs and enables HT analysis of lipid organization and membrane phase behavior.
Liposome Encapsulation Enables Near-Native Cryo-EM Structural Determination by Shielding Macromolecules from Non-Physiological Interfaces.
Gao Zikai, Ma Lijuan, Fu Hang, Yang Chenguang, Ma Dongfei, Zhu Hongtao, Wang Yumei, Sun Dapeng, Hu Shuxin, Xu Chunhua, Ding Wei, Ma Jianbing, Lu Ying, and Li Ming.
bioRxiv posted 10 May 2025.
doi:10.1101/2025.05.06.652550.
Method to improve cryo-EM imaging by encapsulating macromolecular complexes within liposomes.
=> prevents protein denaturation at air-water interfaces, which often skews structural integrity during grid preparation.
=> Improved resolution and native conformations.
Microbio
Emergence and dissemination of multidrug-resistant Klebsiella pneumoniae harboring the novel tmexCD-toprJ RND efflux pump operon.
Gao H, Wang B, Li M, Zhou P, Wu C, Wan C, Shen L, Fu J, Han W, Zhou Y, Yu F.
Front Cell Infect Microbiol. 2025 Apr 30;15:1579880.
doi: 10.3389/fcimb.2025.1579880. eCollection 2025.
PMID: 40370409.
Identification of a new efflux pump operon, tmexCD-toprJ, in multidrug-resistant K. pneumoniae strains isolated in China.
=> high-level resistance to multiple antibiotic classes, including tigecycline. Genomic analysis reveals plasmid-mediated dissemination, raising concern about HGT. 😳😬🫣
The findings call for urgent monitoring and containment of this emerging resistance mechanism.
Bactericidal action of ginger (Zingiber officinale Roscoe) extract against Escherichia coli through synergistic modulation of the AcrAB-TolC efflux pump and inhibition of peptidoglycan synthesis: In vitro and in silico approaches.
Moulick S, Bera R, Roy DN.
Microb Pathog. 2025 Jul;204:107624.
doi: 10.1016/j.micpath.2025.107624. Epub 2025 Apr 21.
PMID: 40268150.
Ginger extract kills E. coli by both inhibiting PG synthesis and disrupting efflux via AcrAB-TolC. Synergistic effects are confirmed through in vitro assays and supported by in silico docking simulations.
Miscellaneous
Physicists turn lead into gold – for a fraction of a second.
Gibney E.
Nature. 2025 May 9.
doi: 10.1038/d41586-025-01484-3. Epub ahead of print.
PMID: 40346331.
Scientists have momentarily transformed lead atoms into gold-like configurations using high-energy collisions in a particle accelerator. The process involves stripping and reconfiguring protons in atomic nuclei, briefly producing gold isotopes.
How quickly do humans mutate? Four generations help answer the question.
Bundell S, Fox D.
Nature. 2025 May 8.
doi: 10.1038/d41586-025-01473-6. Epub ahead of print.
PMID: 40341282.
By sequencing genomes across four generations, researchers calculated the human germline mutation rate => stable rate of ~70 mutations per child, influenced slightly by parental age.
Study also shows that mutation processes vary between individuals and sexes.
Obesity drugs slash some cancer risks
GLP-1s may have anti-cancer effects beyond weight loss alone: GLP-1 agonists can reduce obesity-related cancer risk by up to 50%.
Red Cold Chili Peppers
Identification of Chili Pepper Compounds That Suppress Pungency Perception.
J Agric Food Chem. 2025 May 14.
doi: 10.1021/acs.jafc.5c01448. Epub ahead of print.
PMID: 40365996.
3 ”anti-spice” molecules in chili peppers counteract the heat from capsaicinoids by modulating sensory perception: explains why some chilies are milder than expected.
=> Could lead to tailored chili with controlled spiciness.