MP
Disassembly of the Escherichia coli AcrABZ-TolC efflux pump by ligand-mediated disruption of TolC-AcrA interfacial contacts
Tania Szal, Emmanouela Petsolari, Janis Veliks, Cristina D. Cruz, Laura Paunina, Marina Madre, Fatima-Zahra Rachad, Philipp Lewe, Susanne Witt, Päivi Tammela, Aigars Jirgensons, Ben F. Luisi, Björn Windshügel
bioRxiv 2025.02.18.638599;
doi: https://doi.org/10.1101/2025.02.18.638599
TolC = crucial component of efflux pumps and a potential target for antibiotic adjuvants.
Virtual screen => CEP-37440 = TolC-binding compound that enhances antibiotic efficacy, and further hit deconstruction led to LP-115, which disrupts the TolC-AcrA interface.
Cryo-EM and DLS => suggestion that LP-115 induces TolC closure = novel mechanism for efflux pump inhibition ?
De novo design of transmembrane fluorescence-activating proteins.
Zhu J, Liang M, Sun K, Wei Y, Guo R, Zhang L, Shi J, Ma D, Hu Q, Huang G, Lu P.
Nature. 2025 Feb 19.
doi: 10.1038/s41586-025-08598-8. Online ahead of print.
PMID: 39972138.
Deep learning + energy-based methods to design MPs that specifically bind small molecules.
=> creation of ligand-binding pockets in four-helix backbones for a fluorogenic ligand, achieving high specificity, mid-nanomolar affinity, and enhanced fluorescence compared to GFP.
Structural analyses confirmed the accuracy of the designs.
A new structural paradigm for outer membrane protein biogenesis in the Bacteroidota
Xiaolong Liu, Luis Orenday Tapia, Justin C. Deme, Susan M. Lea, Ben C. Berks
bioRxiv 2025.02.17.638638;
doi: https://doi.org/10.1101/2025.02.17.638638
OM of Gram-negative bacteria = protective barrier, with OMPs inserted by the β-barrel assembly machinery (BAM).
Here: cryo-EM structure of the BAM complex from Flavobacterium johnsoniae => unique architecture differing significantly from E. coli.
This highly modified BAM complex is essential for handling the complex membrane proteins of Bacteroidota, highlighting its specialized role in OM biogenesis.
Discovery of a distinct BAM complex in the Bacteroidetes
Augustinas Silale, Mariusz Madej, Katarzyna Mikruta, Andrew M. Frey, Adam J. Hart, Arnaud Baslé, Carsten Scavenius, Jan J. Enghild, Matthias Trost, Robert P. Hirt, Bert van den Berg
bioRxiv 2025.01.31.636011;
doi: https://doi.org/10.1101/2025.01.31.636011
The BAM complex (essential for outer membrane protein folding in Gram-negative bacteria) is structurally distinct in Bacteroidetes compared to Proteobacteria.
Cryo-EM structures of BAM complexes from Bacteroides thetaiotaomicron and Porphyromonas gingivalis = ∼325 kDa assembly featuring an essential BamF protein and four surface-exposed lipoproteins (BamG-J), forming a large extracellular dome. Unique architecture suggests an expanded functionality in Bacteroidetes.
Not All Bacterial Outer-Membrane Proteins Are β-Barrels.
Heido J, Keng S, Poyrazoglu H, Priyam E, Jayasinghe S.
MicroPubl Biol. 2025 Feb 7;2025:10.17912/micropub.biology.001394.
doi: 10.17912/micropub.biology.001394.
PMID: 39989908.
The discovery of Wza, an octomeric helical barrel integral bacterial outer-transmembrane protein, has challenged the widely held understanding that all integral OMPs of Gram-negative bacteria are closed β-barrels composed of transmembrane β- strands.
Here: bioinformatics analysis suggests that other members of the family may also contain outer-membrane transmembrane segments that are helical.
Outer-membrane core complex proteins of the type IV secretion systems also contain transmembrane segments that are helical.
Structural basis of siderophore export and drug efflux by Mycobacterium tuberculosis.
Earp JC, Garaeva AA, Meikle V, Niederweis M, Seeger MA.
Nat Commun. 2025 Feb 24;16(1):1934.
doi: 10.1038/s41467-025-56888-6.
PMID: 39994240.
MmpL4 and MmpL5 of Mycobacterium tuberculosis secrete mycobactins for iron acquisition and to efflux drugs like bedaquiline and clofazimine, contributing to AMR.
Here: cryo-EM structures of MmpL4 reveal a cytosol-accessible mycobactin binding site essential for both siderophore secretion and drug efflux, along with a unique coiled-coil domain crucial for its function.
In addition, the interaction between MmpL4 and the acyl carrier protein MbtL suggests a direct coupling between mycobactin synthesis and export, highlighting a specialized iron acquisition and drug resistance mechanism in M. tuberculosis.
Exploring the proton transport mechanism of the mitochondrial ADP/ATP carrier: FA-cycling hypothesis and beyond.
Pohl EE, Vazdar M, Kreiter J.
Protein Sci. 2025 Mar;34(3):e70047.
doi: 10.1002/pro.70047.
PMID: 39969060.
Mito ADP/ATP carrier transports ATP, ADP, and protons across the inner mitochondrial membrane, but the exact mechanism of proton transport is debated. It requires uncouplers like long-chain FA or DNP.
Direct proton carrier or anion transporter facilitating FA-cycling, where neutral FA shuttles protons across the membrane ?
Recent findings support the FA-cycling hypothesis, proposing a four-step “sliding” mechanism for FA anion transport, which could extend to other SLC25 family carriers.
Structure Bioinformatics of Six Human Integral Transmembrane Enzymes and their AlphaFold3 Predicted Water-Soluble QTY Analogs: Insights into FACE1 and STEA4 Binding Mechanisms.
Chen E, Pan E, Zhang S.
Pharm Res. 2025 Feb 18.
doi: 10.1007/s11095-025-03822-6. Online ahead of print.
PMID: 39966220.
Structural bioinformatics studies using the QTY code and AlphaFold3 not only provide the opportunities of designing more water-soluble integral membrane enzymes, but also use these water-soluble QTY analogs as antigens for therapeutic monoclonal antibody discovery to specifically target the key integral membrane enzymes.
Membranes
Plasmodesmata act as unconventional membrane contact sites regulating intercellular molecular exchange in plants.
Pérez-Sancho J, Smokvarska M, Dubois G, Glavier M, Sritharan S, Moraes TS, Moreau H, Dietrich V, Platre MP, Paterlini A, Li ZP, Fouillen L, Grison MS, Cana-Quijada P, Immel F, Wattelet V, Ducros M, Brocard L, Chambaud C, Luo Y, Ramakrishna P, Bayle V, Lefebvre-Legendre L, Claverol S, Zabrady M, Martin PGP, Busch W, Barberon M, Tilsner J, Helariutta Y, Russinova E, Taly A, Jaillais Y, Bayer EM.
Cell. 2025 Feb 20;188(4):958-977.e23.
doi: 10.1016/j.cell.2024.11.034.
PMID: 39983675.
In plants, plasmodesmata function as MCSs enabling intercellular communication. This process is regulated by a protein-lipid tethering complex involving multiple C2 domains transmembrane proteins and PI4P, which control docking, plasmodesmata localization, and cell-cell permeability.
Solid-supported polymer-lipid hybrid membrane for bioelectrochemistry of a membrane redox enzyme.
Catania R, Heath GR, Rappolt M, Muench SP, Beales PA, Jeuken LJC.
RSC Appl Interfaces. 2025 Feb 11.
doi: 10.1039/d4lf00362d. Epub ahead of print.
PMID: 39980607.
Hybrid membranes combining PLs and amphiphilic block polymers provide enhanced stability over liposomes and improved biocompatibility compared to polymersomes.
Here: demonstration that solid-supported polymer-lipid hybrid membranes (SSHM) can serve as platforms for membrane protein bioelectrochemistry by reconstituting cyt bo₃ into hybrid vesicles and forming stable SSHMs on gold electrodes.
The bioelectrocatalytic activity of cyt bo₃ was confirmed via cyclic voltammetry, and the longevity of these systems was validated, with SSHMs remaining active even after one year of storage.
Replacement of phenyl substituents at phosphorus by hexyl ones in 2-(2-hydroxyaryl)vinylphosphonium salts can tune the nature of the induced proton transport through lipid membranes.
Rokitskaya TI, Khailova LS, Strelnik AG, Kotova EA, Mironov VF, Tatarinov DA, Antonenko YN.
Biochim Biophys Acta Biomembr. 2025 Feb 19;1867(3):184417.
doi: 10.1016/j.bbamem.2025.184417. Epub ahead of print.
PMID: 39983808.
2-(2-hydroxyaryl)vinylphosphonium salts act as zwitterionic protonophores, facilitating proton transport across lipid membranes via cyclic deprotonation and protonation of the hydroxyl group.
Here: replacing all three phenyl groups at the phosphorus atom with hexyl chains (2HVPHex₃) drastically increases membrane conductance but similar uncoupling activity in mitochondria as phenyl-containing analogs.
Significantly faster mitochondrial swelling => potent protonophoric activity in biological membranes.
Molecules
Lipopolysaccharides nanodiscs, a biomimetic platform to study bacterial surface
Abbas Massilia, Micciulla Samantha, Teulon Jean-Marie, Maalej Meriem, Trembley Macha, Marchetti Roberta, Molinaro Antonio, Thépaut Michel, Fieschi Franck, Pellequer Jean-Luc, Laguri Cédric.
bioRxiv 2025.02.05.636646;
doi: https://doi.org/10.1101/2025.02.05.636646
LPS NDs, formed using SMA copolymers, as biomimetic models of Gram-negative bacterial surfaces for biophysical studies.
Here: high-resolution NMR analysis to study interactions with human C-type Lectin Receptors (CLRs) and polymyxin antibiotics.
=> potential of LPS NDs as valuable tools for investigating bacterial pathogenesis, antimicrobial resistance, and immune system recognition.
Advances in utilizing reverse micelles to investigate membrane proteins.
Walters SH, Birchfield AS, Fuglestad B.
Biochem Soc Trans. 2024 Dec 19;52(6):2499-2511.
doi: 10.1042/BST20240830.
PMID: 39508380.
Reverse micelles (RMs) = nanoscale water-core structures surrounded by surfactants in a non-polar solvent = unique membrane models for studying membrane-associated proteins.
Advances in RM formulations (eg use of phospholipid-based surfactants and natural lipid extracts), have improved their biological accuracy, enabling the encapsulation of diverse membrane proteins such as lipidated and MPs.
Growing importance in biophysical and biochemical research: application of RMs in high-resolution structural studies, protein-membrane interaction analysis, and drug discovery, highlighting their.
Methods
Using Large Language Model to Optimize Protein Purification: Insights from Protein Structure Literature Associated with Protein Data Bank.
Chen Z, Sivaraman J.
Adv Sci (Weinh). 2025 Feb 20:e2413689.
doi: 10.1002/advs.202413689. Epub ahead of print.
PMID: 39976229.
Automated tool using a large language model (LLM) extracts and classifies key data from over 81,000 Protein Data Bank articles to streamline method selection.
Key findings: buffer use (Tris 49.2%), affinity tags (His-tag 82.5%), and E. coli expression conditions (16-20 °C, 12-16 h induction).
Microbio
Self-assembling peptide with dual function of cell penetration and antibacterial as a nano weapon to combat intracellular bacteria.
Zhu Y, Xu W, Chen W, Li B, Li G, Deng H, Zhang L, Shao C, Shan A.
Sci Adv. 2025 Feb 7;11(6):eads3844.
doi: 10.1126/sciadv.ads3844. Epub 2025 Feb 5.
PMID: 39908383.
Self-assembled nanopeptides with dual antibacterial and cell-penetrating functions = promising strategy to combat intracellular bacterial infections and AMR.
Two designed nanopeptides exhibit antibacterial activity, biocompatibility, and effectively eliminate intracellular bacteria while reducing inflammation.
Their mechanism of action involves disrupting bacterial membranes and inducing ROS accumulation, demonstrating significant therapeutic potential and safety in vivo.
Miscellaneous
If you blink at me, I’ll blink back. Domestic dogs’ feedback to conspecific visual cues.
Canori C, Travain T, Pedretti G, Fontani R, Valsecchi P.
R Soc Open Sci. 2025 Feb 19;12(2):241703.
doi: 10.1098/rsos.241703. PMID: 39975663.
Dogs blink more often when they see another dog blink, which could suggest the behaviour plays a role in their communication. Researchers showed 57 adult dogs clips of other dogs blinking, staring ahead, or licking their noses. Some dogs found this exercise boring and fell asleep, but the ones that stayed awake blinked 16% more on average when they watched clips that included blinking. The behaviour might not be a conscious choice, but “could be a way, for example, to signal, ‘I’m relaxed, and you can be, too’”, says ethologist Martina Francesconi.
Based on the science, diversity matters.
Nat Comput Sci. 2025 Feb 19.
doi: 10.1038/s43588-025-00778-w. Epub ahead of print.
PMID: 39972169.
“The evidence is clear: diversity is one of our greatest strengths.”, a must read editorial from Nature Computational Science.
What harm can bias do in groups? Can allyship help?
https://blogs.ubc.ca/allyshipatwork/
Members of advantaged groups can lighten the load of efforts to create a diverse, equitable and inclusive academia — a load that is often disproportionately shouldered by members of disadvantaged groups. It’s worth it: a simulation tool suggests that having even a small proportion of people in a network engaging in allyship actions can foster greater inclusion for those at risk of being marginalized. Behavioural scientist Hsuan-Che ‘Brad’ Huang, and social psychologists Lucy De Souza and Toni Schmader, offer six actionable steps for academics who want to step up to the plate for their colleagues.
Biggest-ever AI biology model writes DNA on demand.
Callaway E.
Nature. 2025 Feb 19.
doi: 10.1038/d41586-025-00531-3. Epub ahead of print.
PMID: 39972093.
Scientists have unveiled Evo-2, an artificial-intelligence (AI) model that can write whole chromosomes and small genomes from scratch. The model — which was trained on 128,000 genomes spanning the tree of life, from humans to single-celled bacteria and archaea — can also make sense of existing DNA, including hard-to-interpret ‘non-coding’ gene variants that are linked to disease. Researchers seem impressed by what they’ve read about Evo-2, but note that they’ll need to try it for themselves before coming to firm conclusions.
Periodic cooking of eggs.
Di Lorenzo E, Romano F, Ciriaco L, Iaccarino N, Izzo L, Randazzo A, Musto P, Di Maio E.
Commun Eng. 2025 Feb 6;4(1):5.
doi: 10.1038/s44172-024-00334-w.
PMID: 39915675.
How to cook the perfect boiled egg, according to science !
The perfect boiled egg is a matter of simply placing it alternately in boiling and tepid (30 ℃) water eight times for a total of 32 minutes, say researchers seeking the elusive velvety yolk and soft, solid white.
How AI is revealing the language of the birds.
Bates E.
Nature. 2025 Feb 21. doi: 10.1038/d41586-025-00539-9.
Epub ahead of print.
PMID: 39984689.
Researchers have been eavesdropping on unusually close-knit families of carrion crows (corvus corone corone) in Spain, collecting data on hundreds of thousands of different vocalizations. Small microphones recorded a variety of soft calls, far quieter than the familiar ‘caws’. The team then used AI to analyse and group the sounds. The researchers aim to better understand how the crows cooperate — and experiment with some human-crow chats.
The 2025 Guthman Musical Instrument Competition
The Guthman Musical Instrument Competition is a competition new ideas in music. On March 7 and 8, 2025, ten finalists from around the world will showcase the next generation of musical instruments.
Here are their musical and design !
I vote for “3 Axis MIDI Guitar”, “Hacked Double Trumpet” (🇫🇷🐓) and ”Mulatar” ! What about you ?