MP

Ca2+-pumping by PMCA-neuroplastin complexes operates in the kiloHertz-range.

Constantin CE, Schmidt B, Schwarz Y, Harada H, Kollewe A, Müller CS, Henrich S, Gaal B, Kulik A, Bruns D, Schulte U, Rieger H, Fakler B.

Nat Commun. 2025 Aug 20;16(1):7550. 

doi: 10.1038/s41467-025-62735-5.

PMID: 40835599.

PMCA-neuroplastin complex can pump Ca²⁺ at kilohertz frequencies in neurons. 

Electrophysiology and computational models => rapid calcium clearance during intense synaptic activity. Neuroplastin stabilizes the PMCA complex and is essential for its function. 

Explains how neuronal calcium homeostasis is maintained at high firing rates.

A structural and functional bioinformatics study of QTY-designed retinylidene proteins.

Pan S.

QRB Discov. 2025 Jul 14;6:e20. 

doi: 10.1017/qrd.2025.10009. eCollection 2025.

PMID: 40838111. 

How QTY design enables solubilization of hydrophobic retinylidene MPs. 

Substitution of hydrophobic residues with Q, T, and Y => proteins become water-soluble while retaining key functional features. 

Structural modeling suggests that retinal binding pockets and photoactivation residues remain intact.

Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters.

Zhang Z, Maharjan R, Gregor WD, Klenotic PA, Yu EW.

Sci Adv. 2025 Aug 15;11(33):eadx1129. 

doi: 10.1126/sciadv.adx1129. Epub 2025 Aug 13.

PMID: 40802754.

Cryo-EM structures of MmpL transporters => modular architecture with dynamic conformations enabling substrate capture and release. 

Identification of conserved motifs critical for proton coupling and lipid recognition.

 A new class of binding-protein dependent solute transporter exemplified by the TAXI-GltS system from Bordetella pertussis.

Jaques LM, Davies JFS, Sheldon-Towler JJ, Kelly DJ, Leone V, Mulligan C.

Commun Biol. 2025 Aug 12;8(1):1201. 

doi: 10.1038/s42003-025-08591-x.

PMID: 40797014. 

New class of binding protein-dependent solute transporters exemplified by the TAXI-GltS system in Bordetella pertussis. 

Structural and functional studies reveal how the TAXI protein presents glutamate to GltS for import (a bipartite transporter design ≠ from classical ABC or TRAP systems).

SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport.

Benedikt T Kuhn, Peter Kovermann, Bassam G Haddad, Tim Rasmussen, Tamsanga Hove, Stefanie Bungert-Pluemke, Bettina Boettcher, Jan-Philipp Machtens, Christoph Fahlke, and Eric R. Geertsma.

bioRxiv posted 19 August 2025 doi:10.1101/2025.08.17.670773.

SLC26A11 as a lysosomal sulfate transporter + ion channel-like behavior. 

Cryo-EM structures => architecture enabling dual transport and conductive properties. 

Functional assays in lysosomal environments. 

Structure and function of the human apoptotic scramblase Xkr4.

Chakraborty S, Feng Z, Lee S, Alvarenga OE, Panda A, Zhang S, Bruni R, Khelashvili G, Gupta K, Accardi A.

Nat Commun. 2025 Aug 8;16(1):7317. 

doi: 10.1038/s41467-025-62739-1.

PMID: 40781244.

Cryo-EM structure of human Xkr4 (scramblase activated during apoptosis).

Upon caspase cleavage, the protein undergoes conformational changes that allow phospholipid scrambling. 

Constitutive lipid scramblase activity underpins mechanosensitive TMEM63 channelopathies.

Brynn R, Poole K.

Neuron. 2025 Aug 6;113(15):2373-2375. 

doi: 10.1016/j.neuron.2025.07.004.

PMID: 40774124.

Link between constitutive scramblase activity of TMEM63 channels to mechanosensitive diseases. 

Disruption of lipid asymmetry => dysfunctional ion channel activity. 

The authors propose that aberrant lipid scrambling contributes to TMEM63-related pathologies.

Opsins are Phospholipid Scramblases in All Domains of Life.

Zachary A Maschmann, David E Hardy, Indu N Menon, Jenna L Webb, Anant K Menon, and Katrina T Forest.

bioRxiv posted 18 August 2025.

doi:10.1101/2025.08.17.670764.

Opsins function as phospholipid scramblases across all domains of life. 

Activity occurs independently of light, challenging the classical view of opsins as solely photoreceptors. 

Conserved structural features support a dual-function mechanism. 

Suggest an ancient evolutionary link between light sensing and membrane dynamics.

Inhibiting heme piracy by pathogenic Escherichia coli using de novo-designed proteins.

Fox DR, Asadollahi K, Samuels I, Spicer BA, Kropp A, Lupton CJ, Lim K, Wang C, Venugopal H, Dramicanin M, Knott GJ, Grinter R.

Nat Commun. 2025 Jul 9;16(1):6066. 

doi: 10.1038/s41467-025-60612-9.

PMID: 40634285.

de novo proteins engineered to bind heme with high specificity to prevent uptake by pathogenic E. coli. 

=> block heme acquisition under iron-limiting conditions, impairing bacterial growth. Structural data confirm tight binding and stability.

The molecular mechanism of lipid uptake by membrane-anchored bridge-like lipid transfer proteins.

Daniel Alvarez, Paige Chandran Blair, Cristian Rocha-Roa, Michael Davey, Elizabeth Conibear, and Stefano Vanni.

bioRxiv posted 2 August 2025. 

doi:10.1101/2025.08.01.668188.

How bridge-like lipid transfer proteins facilitate lipid movement between membranes. 

Simulations and experiments => proteins span donor and acceptor membranes via a hydrophobic tunnel. 

Conformational gating controls tunnel opening, modulating lipid flow.

Computational design of allosteric pathways reprograms ligand-selective GPCR signaling.

Mahdi Hijazi, Daniel Keri, Aurelien Oggier, Aditya Sengar, Melina A Agosto, Theodore G. Wensel, and Patrick Barth.

bioRxiv posted 18 August 2025. 

doi:10.1101/2025.08.13.670154.

Computational design to reprogram GPCR allosteric signaling pathways. 

Alteration of internal networks => ligand-selective signaling bias. 

MD and mutational studies validate the designs.

An Orchestrated Interaction Network at the Binding Site of Human SERT Enables the Serotonin Occlusion and Import.

Zhao Z, Wen PC, Tajkhorshid E.

Biochemistry. 2025 Aug 19;64(16):3652-3662. 

doi: 10.1021/acs.biochem.5c00240. Epub 2025 Jul 28.

PMID: 40722230.

Dissection of the molecular interactions enabling serotonin binding and transport by human SERT. 

Simulations => coordinated network that traps serotonin in an occluded conformation.

Membranes

Structural basis for membrane microdomain formation by a human Stomatin complex.

Stoner J, Li S, Fu Z.

Nat Commun. 2025 Aug 12;16(1):7439. 

doi: 10.1038/s41467-025-62859-8.

PMID: 40796562. 

Structure of a human stomatin complex involved in membrane microdomain formation. 

=> shows how oligomeric stomatin assemblies create lateral membrane organization through lipid interaction and scaffolding. 

Structural data suggest a mechanism for modulating membrane curvature and protein localization.

Structural molecular details of the endocytic adaptor protein CALM upon binding with phosphatidylinositol 4,5-bisphosphate-containing model membranes. 

Santamaria A, Pereira D, Pawar N, Kelly BT, Carrascosa-Tejedor J, Sardo M, Mafra L, Fragneto G, Owen DJ, Marín-Montesinos I, Guzmán E, Zaccai NR, Maestro A.

Commun Chem. 2025 Jul 29;8(1):219. 

doi: 10.1038/s42004-025-01590-3. 

PMID: 40730637.

Investigate how the adaptor protein CALM interacts with PIP2-containing membranes using ssNMR and modeling. 

CALM adopts a distinct conformation allowing interaction with both lipid headgroups and acyl chains => stabilize CALM in a membrane-associated state compatible with endocytosis. 

=> clarifies how CALM contributes to vesicle formation and cargo recognition.

Characterization of Aquaporin Z proteoliposome structure and functionality via microscopy and scattering methods.

Szathmáry ZE, Pedersen MC, Michels A, Regueira THB, Kirkensgaard JJK.

Eur Biophys J. 2025 Aug 7. 

doi: 10.1007/s00249-025-01790-8. Online ahead of print.

PMID: 40773014.

cryo-TEM and scattering methods to assess structure and function of AqpZ reconstituted in proteoliposomes. 

=> preserved liposome integrity and functional water transport through the embedded channels. 

=> demonstrates how biophysical techniques validate reconstitution success.

Advances in native cell membrane nanoparticles system.

Qiu W, Guo Y.

Curr Opin Struct Biol. 2025 Aug 6;94:103130. 

doi: 10.1016/j.sbi.2025.103130. Online ahead of print.

PMID: 40774150.

Review on advances in native cell membrane nanoparticle (NCMNP) systems for studying MPs. 

=> improved methods for extracting and stabilizing proteins within their endogenous lipid environments. Applications: cryo-EM, immunology, drug screening … 

Surface-attached model lipid membranes derived from human red blood cells.

Sanyukta Prakash Mudakannavar, Matthew D Mitchell, and Robert J Rawle.

bioRxiv posted 18 August 2025.

doi:10.1101/2025.08.18.670922.

Method to create supported lipid bilayers from RBC-derived lipids. 

=> maintain native lipid complexity and exhibit realistic fluidity and phase behavior. 

=> compatible with optical and spectroscopic tools.

Molecules

Design of zwitterionic fluorescent polymers for membrane protein solubilization into native nanodiscs.

Overduin M, Kuyler GC, Esmaili M, Trieber CA, Acevedo-Morantes C, Orazietti AP, Shaykhutdinov R, Bhat RK, Omotoso T, Tajammul S, Rahim M, Zinn-Justin S, Bishop RE, Prosser RS, Wille H, Klumperman B.

Biophys Chem. 2025 Jul 9;325:107489. doi: 10.1016/j.bpc.2025.107489. Online ahead of print.

PMID: 40652574.

Novel zwitterionic fluorescent polymers that solubilize MPs into NDs while preserving their native lipid surroundings. 

=> solubilization efficiency and compatibility with fluorescence-based applications. 

Functional reconstitution of transporters and GPCRs confirms bioactivity retention. 

Solubilization and refolding of inclusion bodies by detergents.

Arakawa T, Akuta T, Ejima D, Tsumoto K.

Protein Expr Purif. 2025 Aug 7:106791. 

doi: 10.1016/j.pep.2025.106791. Online ahead of print.

PMID: 40783056. 

Detergent-based protocol for solubilizing and refolding proteins from bacterial inclusion bodies. 

The method optimizes yield and folding efficiency across various aggregation-prone proteins. 

Deuterated Detergents for Structure-Function Analysis of Membrane Proteins in Solution Using Nuclear Magnetic Resonance (NMR) Spectroscopy and Small-Angle Neutron Scattering (SANS).

Kazumi Hiruma-Shimizu, Hiroki Shimizu, Nighat Nawaz, Gary S. Thompson, Jennifer H. Tomlinson, Arnout P. Kalverda, Simon G. Patching.

Scholars International Journal of Chemistry and Material Sciences

ISSN 2616-8669 (Print) |ISSN 2617-6556 (Online)

https://doi.org/10.36348/sijcms.2025.v08i04.001

Use of deuterated detergents for structural studies of membrane proteins by NMR and SANS. 

These detergents reduce background signal, improve contrast and enable detailed structural insights into MPs in solution.

Nanodisc-reconstitution for single particle cryo-EM structure determination of membrane proteins. 

Grant AJ, Schmidt-Krey I.

Curr Opin Struct Biol. 2025 Aug;93:103072. 

doi: 10.1016/j.sbi.2025.103072. Epub 2025 May 28. 

PMID: 40446521.

Methods

Assessing Protein-Lipid Interactions with a Low-Cost, Accessible Centrifugation Assay.

Villaseñor CG, Karagiaridi A, Dimitrova VS, Buyco DG, Candal I, Smirnova A, Pinkett HW, Kamat NP.

Biophys Rep (N Y). 2025 Jul 25:100224. 

doi: 10.1016/j.bpr.2025.100224. Online ahead of print.

PMID: 40716612.

Low-cost centrifugation assay to quantify protein–lipid interactions using vesicle binding. 

The method distinguishes bound from unbound protein via supernatant/pellet analysis, requiring only basic laboratory equipment. 

Compatible with both peripheral and integral MPs.

Simple and rapid TLC blotting-based methodology for screening membrane protein-specific lipids.

Wangamnuayporn S, Matsumori N.

Anal Sci. 2025 Aug 19. 

doi: 10.1007/s44211-025-00841-6. Online ahead of print.

PMID: 40828288.

TLC blotting method to screen MP-specific lipid interactions. Proteins immobilized on membranes are incubated with TLC-separated lipid extracts, allowing detection of preferred binding partners.

One-Pot Reconstitution of GPCRs into Unilamellar Vesicles for Fluorescence-Based Phospholipid Scramblase Activity Assay.

Menon I, Menon AK.

Methods Mol Biol. 2025;2958:255-269. 

doi: 10.1007/978-1-0716-4714-1_17.

PMID: 40833579.

One-pot protocol for reconstituting GPCRs into unilamellar vesicles and measuring their scramblase activity. 

=> fluorescence quenching to detect PL scrambling across the membrane. 

High-speed AFM imaging of the Entropic Disassembly of DNA Origami for Single-Molecule Biosensing.

Chalmers Chi Chau, Varun Gupta, George R Heath, Christoph Walti, and Paolo Actis.

bioRxiv posted 19 August 2025 

doi:10.1101/2025.08.15.670511.

High-speed AFM to visualize disassembly of DNA origami structures in real time. 

Ligand binding => nanoscale changes in DNA structure can be observed at the single-molecule level. 

Setup and Evaluation of the TRACT Assay Principle for the In Vitro Functional Characterization of Modulators of the Serotonin Transporter and the Serotonin 2A Receptor.

Timmerman A, Walther D, Baumann MH, Gréen H, Pottie E, Stove CP.

Anal Chem. 2025 Aug 19;97(32):17872-17881. 

doi: 10.1021/acs.analchem.5c03836. Epub 2025 Aug 6.

PMID: 40767848.

TRACT assay to study functional modulation of serotonin-related receptors => activity of serotonin transporter (SERT) and 5-HT2A receptor in vitro. 

Enables parallel characterization of ligand effects on transport and signaling.

Microbio

Coordination of virulence factors and lifestyle transition in Pseudomonas aeruginosa through single-cell analysis. 

Chen H, Malengo G, Wang L, Vogler O, Renner M, Glatter T, Paczia N, Unterweger D, Sourjik V, Diepold A.

Commun Biol. 2025 Aug 16;8(1):1236. 

doi: 10.1038/s42003-025-08693-6. 

PMID: 40819180.

Single-cell transcriptomics to explore how P. aeruginosa shifts between virulence and biofilm lifestyles. 

=> subpopulations with distinct expression profiles for secretion systems, motility, and quorum sensing. These states are environmentally responsive and mutually exclusive.

Extracellular defense of bacteria against antimicrobial peptides.

Fleitas O, Rebollar EA, Bustamante VH.

J Bacteriol. 2025 Aug 1:e0016625. 

doi: 10.1128/jb.00166-25. Online ahead of print.

PMID: 40748075. 

Review how bacteria defend themselves extracellularly against host antimicrobial peptides : secretion of decoys, surface binding, peptide degradation … 

Strategies act in concert with intracellular resistance systems like efflux or enzymatic modification.

Evaluating the Link between Efflux Pump Expression and Motility Phenotypes in Pseudomonas aeruginosa Treated with Virulence Inhibitors.

Lembke HK, Nauta KM, Hunter RC, Carlson EE.

ACS Infect Dis. 2025 Aug 8;11(8):2080-2089. 

doi: 10.1021/acsinfecdis.5c00053. Epub 2025 Apr 27.

PMID: 40287835.

Impact of virulence inhibitors on motility and efflux systems in P. aeruginosa. 

Inhibiting virulence = > alteration of swarming and swimming behavior + modulation of the  expression of efflux pumps. 

This suggests a regulatory interplay between motility and antibiotic resistance.

Miscellaneous

How did life get multicellular? Five simple organisms could have the answer. 

Katsnelson A.

Nature. 2025 Aug;644(8078):856-859. 

doi: 10.1038/d41586-025-02635-2. 

PMID: 40866691.

Across all forms of life, the move from being single-celled to multicellular seems to have happened dozens of times — for animals, though, the jump was one-and-done. The unique cocktail of environmental and genetic factors that helped animal ancestors make that jump still eludes our understanding. To investigate, researchers are focussing on unicellular organisms that ‘dabble’ in multicellularity, occasionally forming colonies of many cells. By studying these organisms as they flit between the two states, scientists are hoping to illuminate how multicellularity stuck in animals — and what sparked the single successful event that gave rise to the animal kingdom.

Post K-Pg rise in ant and termite prevalence underlies convergent dietary specialization in mammals. 

Vida T, Calamari ZT, Barden P. 

Evolution. 2025 Jun 2:qpaf121. 

doi: 10.1093/evolut/qpaf121. Epub ahead of print. 

PMID: 40455576.

Mammals have evolved into forms specialized to eat ants and termites at least 12 separate times over the last 66 million years. Their appearances might have been driven by a boom in ant and termite populations after the dinosaurs went extinct, researchers say. And evolution doesn’t discriminate — ant-eating animals have popped up among marsupials, egg-laying mammals and placental mammals. “Things keep evolving into anteaters, somehow,” says palaeontologist and study co-author Thomas Vida.

These genes can have the opposite effects depending on which parent they came from. 

Fieldhouse R. 

Nature. 2025 Aug 7. 

doi: 10.1038/d41586-025-02499-6. Epub ahead of print. 

PMID: 40770562.

The effect of a gene can vary greatly — and sometimes be the complete opposite — depending on which parent it’s inherited from. A team of researchers have devised a statistical model that has revealed at least 30 of these parent-of-origin effects in 14 genes, all without needing genomic data from a person’s parents. Nineteen gene variants had a ‘bipolar effect’, meaning it had opposite effects depending on which parent it came from. One such variant increased the risk of developing type 2 diabetes by 14% when inherited from the father but decreased it by 9% when inherited from the mother.

Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease. 

Yuan X, Nie S, Yang Y, Liu C, Xia D, Meng L, Xia Y, Su H, Zhang C, Bu L, Deng M, Ye K, Xiong J, Chen L, Zhang Z.

Nat Neurosci. 2025 Mar;28(3):577-588. 

doi: 10.1038/s41593-024-01866-2. Epub 2025 Jan 23. 

PMID: 39849144.

Misfolded α-synuclein can spread from the kidney to the brain in animal models. The aggregates initiate Parkinson-like pathology, supporting a peripheral origin in some cases.