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20250415_Membrane’s digest

MP

Cryo-EM structure of the bacterial intramembrane metalloprotease RseP in the substrate-bound state.

Asahi K, Hirose M, Aruga R, Shimizu Y, Tajiri M, Tanaka T, Adachi Y, Tanaka Y, Kaneko MK, Kato Y, Akashi S, Akiyama Y, Hizukuri Y, Kato T, Nogi T.

Sci Adv. 2025 Feb 28;11(9):eadu0925. 

doi: 10.1126/sciadv.adu0925. Epub 2025 Feb 26.

PMID: 40009668.

Cryo-EM structure of the bacterial intramb protease RseP in complex with its substrate: insight into post-translational regulation during bacterial envelope stress responses. 

=> RseP recognizes substrates via a “tail-length sensing” mechanism coupled with specific interactions. 

=> key conformations enabling the cleavage of membrane-anchored substrates.


Membranes

Membrane Transport Modulates the pH-Regulated Feedback of an Enzyme Reaction Confined within Lipid Vesicles.

Ridgway-Brown D, Leathard AS, France O, Muench SP, Webb ME, Jeuken LJC, Henderson PJF, Taylor AF, Beales PA.

ACS Nano. 2025 Mar 3. 

doi: 10.1021/acsnano.4c13048. Online ahead of print.

PMID: 40029853.

Study exploring how membrane transport modulates an enzyme reaction confined within lipid vesicles, i.e how intracellular microenvironments influence biochemical reactions. 

=> proton fluxes regulate a pH-dependent feedback on enzymatic activity. Simulations and experiments confirm that membrane permeability is a critical parameter.


Methods

Development of ultra-miniaturized weak affinity chromatography coupled to mass spectrometry as a high throughput fragment screening method against wild-type and purified membrane proteins embedded in biomimetic membranes.

Vidal FX, Gil J, Gregson M, Zeder-Lutz G, Hideux M, Lemoine J, Krimm I, Wagner R, Dugas V, Demesmay C.

Anal Chim Acta. 2025 Jun 1;1353:343950. 

doi: 10.1016/j.aca.2025.343950. Epub 2025 Mar 17.

PMID: 40221197

Novel method combining miniaturized weak affinity chromatography and MS (nano-WAC-MS) to screen fragments for weak binding to a MPs in NDs.

=> minimal protein amounts and HT analysis (up to 150 fragments per run), even with high DMSO content. 

=> approach validated by comparing results to NMR and other binding assays, showing that it offers a robust and reusable platform for fragment screening against MPs.


Rapid quantification of intracellular calcium stores reveals effects of membrane micropeptides on SERCA function.

Cunningham JD, Phillips TA, Seflova J, Cho EE, Robia SL.

Cell Calcium. 2025 Mar;126:103000. doi: 10.1016/j.ceca.2025.103000. Epub 2025 Feb 7.

PMID: 39921961

Rapid method to quantify intracellular calcium stores, crucial for understanding cell signaling. Technique applied to assess how membrane micropeptides affect the activity of the SERCA pump (certain micropeptides alter SERCA’s affinity for calcium) => subtle regulatory mechanisms.


Alanine Scanning to Define Membrane Protein-Lipid Interaction Sites Using Native Mass Spectrometry.

Jayasekera HS, Mohona FA, De Jesus MJ, Miller KM, Marty MT.

Biochemistry. 2025 Mar 6. doi: 10.1021/acs.biochem.4c00717. Online ahead of print.

PMID: 40047061

Native mass spectrometry to map membrane protein–lipid interactions through alanine scanning => specific residues involved in lipid anchoring are identified. 

It provides key structural insights without requiring crystallization => new possibilities for studying protein–lipid interfaces under near-native conditions.


AFsample2 predicts multiple conformations and ensembles with AlphaFold2.

Kalakoti Y, Wallner B.

Commun Biol. 2025 Mar 5;8(1):373. 

doi: 10.1038/s42003-025-07791-9.

PMID: 40045015.

AFsample2 = tool derived from AF2 that predicts not only a single protein structure but also conformational ensembles. 

=> allows exploration of structural flexibility and functional dynamics. The model improves the prediction of alternative structures often key for protein interactions.


In Silico Study of a Bacteriorhodopsin/TiO2 Hybrid System at the Molecular Level.

Avelar M, Coppola C, d’Ettorre A, Ienco A, Parisi ML, Basosi R, Santucci A, Olivucci M, Sinicropi A.

J Chem Theory Comput. 2025 Mar 4. 

doi: 10.1021/acs.jctc.4c01370. Online ahead of print.

PMID: 40037620

Simulation of the dynamics of a hybrid system made of BR bound to TiO₂. This interaction is shown to alter the electronic states and photoactivation of the protein. 

This system is relevant for for designing bio-inspired devices: bioelectronic or photovoltaic applications.


Expanding the diversity of nitroxide-based paramagnetic probes conjugated to non-canonical amino acids for SDSL-EPR applications.

Bizet M, Balazsi A, Biaso F, Byrne D, Etienne E, Guigliarelli B, Urban P, Dorlet P, Truan G, Gerbaud G, Kalai T, Martinho M.

Chembiochem. 2025 Feb 26:e202500064. 

doi: 10.1002/cbic.202500064. Online ahead of print.

PMID: 40011209.

New nitroxide-based paramagnetic probes tailored for spin-labeling EPR spectroscopy. These probes are conjugated to non-canonical amino acids to target specific protein sites. Their chemical diversity enables better exploration of protein structural dynamics.


Microbio

Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa.

Yamasaki S, Koga N, Nakashima R, Hayashi-Nishino M, Nishino K.

Biol Pharm Bull. 2025;48(3):230-233. 

doi: 10.1248/bpb.b23-00190.

PMID: 40024693.

Analysis of point mutations in the MexB efflux pump from clinical isolates of Pseudomonas aeruginosa => variants altering antibiotic susceptibility. These mutations affect substrate transport and contribute to resistance. 

=> need to monitor MexB variants to improve treatment strategies.


Targeting efflux pumps prevents the multi-step evolution of high-level resistance to fluoroquinolone in Pseudomonas aeruginosa

Yu X-Q, Yang H, Feng H-Z, Hou J, Tian J-Q, Niu S-M, You C-G, Tao X-Y, Zhang S-P, Wang Z-P, He Y-X.

Microbiol Spectr. 2025 Feb 21:e0298124. 

doi: 10.1128/spectrum.02981-24. Epub ahead of print. 

PMID: 39982069.

Targeting efflux pumps prevents the multi-step development of high-level fluoroquinolone resistance in Pseudomonas aeruginosa. Authors show that pump inhibition blocks successive adaptation stages => antivirulence strategy to complement classical antibiotics.


Outer membrane permeability of Pseudomonas aeruginosa through β-lactams: new evidence on the role of OprD and OpdP porins in antibiotic resistance.

Amisano F, Mercuri P, Fanara S, Verlaine O, Motte P, Frère JM, Hanikenne M, Galleni M.

Microbiol Spectr. 2025 Mar 4:e0049524. 

doi: 10.1128/spectrum.00495-24. Online ahead of print.

PMID: 40035575.

Reassessement of the roles of OprD and OpdP porins in Pseudomonas aeruginosa permeability to β-lactams. 

=> these porins contribute differently to antibiotic uptake depending on context (≠ from simplified models of resistance due to OprD loss alone).


Determination of Pseudomonas aeruginosa MexXY-OprM substrate profile in a major efflux knockout system reveals distinct antibiotic substrate classes.

Kavanaugh LG, Hariharan SM, Conn GL.

Microbiol Spectr. 2025 Mar 4;13(3):e0290324. 

doi: 10.1128/spectrum.02903-24. Epub 2025 Feb 6.

PMID: 39912696.

This study uses a P. aeruginosa strain lacking major efflux systems to characterize the substrate specificity of MexXY-OprM. 

Identification of distinct antibiotic classes based on their export profiles. This substrate mapping helps predict the efficacy of combination therapies.


Importance of the envelope in Escherichia coli resistance to lithium.

Fierling N, Billard P, Dluzniewski A, Sohm B, Bauda P, Blaudez D.

Chemosphere. 2025 Apr;374:144234. 

doi: 10.1016/j.chemosphere.2025.144234. Epub 2025 Feb 20.

PMID: 39983623.

Investigate of lithium resistance in Escherichia coli, an underexplored mechanism of ionic toxicity.

=> the cell envelope plays a central role (mutants with defects in the wall or membrane are more sensitive). Lithium appears to selectively disrupt the cell barrier.


Miscellaneous

Immunotherapy: a molecule from a pioneering technology co-invented by the Institut Curie and Biomunex.

https://curie.fr/actualite/transfert-de-technologie/immunotherapie-une-molecule-issue-dune-technologie-pionniere

BMX-502 = bispecific antibody that engages and activates MAIT cells (or “Mucosal Associated Invariant T-cells”) and targets the tumor antigen GPC3 – a clinically validated target, highly expressed in several types of cancer – to destroy tumor cells.


Can AI help to end poverty?

Arnold C.

Nature. 2025 Feb;638(8052):878-880. 

doi: 10.1038/d41586-025-00565-7. 

 PMID: 40011727.

Quashing poverty requires knowing who is in need and what their needs are but collecting those data has long been a time-consuming and costly challenge. Some researchers are turning to artificial intelligence (AI) tools to help plug the gaps. AI can be biased and could miss people without a digital trail. On the other hand it can analyse a larger more representative portion of the population than do household surveys and identify patterns in data that even specialists could miss says development economist Ariel BenYishay.


The cake factor

https://themeta.news/cake-factor/

What if the best way to evaluate labs were the number of cakes shared, in proportion to everyone’s goodwill in celebrating the publication of a paper or the receipt of funding? In Times Higher Education, Norway’s Mats Persson and Sweden’s Jan Ch. Karlsson propose the Cake-factor. A tradition which, they say, “strengthens organizational culture and recognizes the hard work of authors”.