Membrane’s digest

MP

Excitation energy transfer in proteoliposomes reconstituted with LH2 and RC-LH1 complexes from Rhodobacter sphaeroides.

Huang X, Vasilev C, Swainsbury DJ, Hunter CN.

Biosci Rep. 2024 Jan 16:BSR20231302.

doi: 10.1042/BSR20231302.

LH2 and RC-LH1 purified from  Rhodobacter sphaeroides reconstituted into proteoliposomes either separately, or together at three different LH2:RC-LH1 ratios, for excitation energy transfer studies. AFM used to investigate the distribution and association of the complexes. Absorption and fluorescence emission spectra were similar for LH2 complexes in detergent and liposomes, indicating that reconstitution retains the structural and optical properties of the LH2 complexes.

 

AlphaFold2-guided description of CoBaHMA, a novel family of bacterial domains within the heavy-metal-associated superfamily.

Gaschignard G, Millet M, Bruley A, Benzerara K, Dezi M, Skouri-Panet F, Duprat E, Callebaut I.

Proteins. 2024 Jan 22. doi: 10.1002/prot.26668.

3D structure information = facilitation of the detection of remote evolutionary relationships in protein superfamilies.

Here: identification of a novel family of protein domains related to the ferredoxin-like superfold.

Heavy-metal-associated superfamily share conserved basic amino acids (CoBaHMA = Conserved Basic residues HMA) => positively charged surface to interact with anionic partners. CoBaHMA domains are found in diverse modular organizations in bacteria some of which are MPs involved in transport or lipid metabolism (interactions with anionic lipids).

 

Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2.

Kreiter J, Tyschuk T, Pohl EE.

Biomolecules. 2023 Dec 22;14(1):21.

doi: 10.3390/biom14010021.

High homology between UCP2 and UCP3 => hypothesis that UCP3 transports C4 metabolites similar to UCP2 => measure of the transport of substrates against phosphate (32Pi) in proteoliposomes reconstituted with recombinant murine UCP3 (mUCP3).

mUCP3 mainly transports aspartate and sulfate but also malate, malonate, oxaloacetate, and succinate (transport rates calculated from the exchange of 32Pi / aspartate and sulfate = 23.9 and 17.5 µmol/min/mg, respectively.

 

High-throughput computational screening for identification of potential hits against bacterial Acriflavine resistance protein B (AcrB) efflux pump.

Rathod S, Dey S, Choudhari P, Mahuli D, Rochlani S, Dhavale R, Chaudhari S, Tamboli Y, Kilbile J, Rajakumara E.

J Biomol Struct Dyn. 2024 Jan 24:1-17.

doi: 10.1080/07391102.2024.2302936.

Multi-approached computational screening strategy (molecular docking, in silico ADMET analysis, druglikeness assessment, MD simulations and density functional theory studies) to identify novel hits capable of acting against AcrB-mediated antibiotic resistance.

 

Molecular Modeling Studies to Probe the Binding Hypothesis of Novel Lead Compounds against Multidrug Resistance Protein ABCB1.

Cheema Y, Linton KJ, Jabeen I.

Biomolecules. 2024 Jan 16;14(1):114.

doi: 10.3390/biom14010114.

Docking of inhibitors into a model structure of human ABCB1 (=P-gp) and use of MD to report its conformational dynamics induced by the binding of the inhibitors.

 

Probing the allosteric NBD-TMD crosstalk in the ABC transporter MsbA by solid-state NMR.

Novischi SYP, Karoly-Lakatos A, Chok K, Bonifer C, Becker-Baldus J, Glaubitz C.

Commun Biol. 2024 Jan 5;7(1):43.

doi: 10.1038/s42003-023-05617-0.

ABC transporter MsbA => translocates core-LPS across the IM and + broad substrate specificity for lipophilic drugs.

The allosteric interplay between substrate binding (in TMD) and ATP binding must be mediated via the NBD/TMD interface. Previous studies suggested the involvement of coupling helix 1 and 2 (CH1, CH2).

Here: ssNMR spectroscopy => substantial chemical shift changes within CH1 and CH2 upon substrate binding, in the ATP hydrolysis transition state, and upon inhibitor binding. CH2 is domain-swapped within the MsbA structure, and substrate binding induces a larger response in CH2 compared to CH1.

 

Membranes

Lipid osmosis, membrane tension, and other mechanochemical driving forces of lipid flow.

Zhang Y, Lin C.

bioRxiv [Preprint]. 2024 Jan 8:2024.01.08.574656.

doi: 10.1101/2024.01.08.574656.

Nonvesicular lipid transport = crucial in lipid homeostasis or organelle biogenesis. However, the forces that drive such lipid transport are not well understood.

Here: they propose that lipids tend to flow towards the membrane area with a higher MP density in a process termed lipid osmosis . This process lowers the membrane tension in the area when the lipid flow reaches equilibrium.

=> thermodynamic basis and experimental evidence of lipid osmosis and the corresponding osmotic membrane tension.

 

A comparative study of influenza A M2 protein conformations in DOPC/DOPS liposomes and in native E. coli membranes.

Sanders G, Borbat PP, Georgieva ER.

bioRxiv [Preprint]. 2024 Jan 9:2024.01.08.574681.

doi: 10.1101/2024.01.08.574681.

Comparison of the conformations of the TMD of influenza A M2 protein (IAM2) reconstituted at pH 7.4 in DOPC/DOPS bilayers or in isolated E. coli membranes (electron spin resonance study, CW and DEER).

=> IAM2 TMD has similar conformations in model and native E. coli membranes of comparable thickness and fluidity.

 

Molecules

Capturing G protein-coupled receptors into native lipid-bilayer nanodiscs using new diisobutylene/maleic acid (DIBMA) copolymers

Ci Chu, Carolyn Vargas, MariaCarolina Barbosa, Simon Sommerhage, Gnnar F. Schröder, Sandro Keller, Manuel Etzkorn

bioRxiv 2024.01.20.576420; 

doi: https://doi.org/10.1101/2024.01.20.576420

SMA and DIBMA polymers have drawbacks that limit their application (high negative charge densities, which can interfere with protein–protein and protein–lipid interactions).

Here: series of new amphiphilic copolymers derived from DIBMA via partial amidation of the carboxylate pendant groups with various biocompatible amines. Properties of the new polymers assessed using model membranes as well as in the context of extracting the melanocortin 4 receptor (MC4R), a prototypical class A GPCR.

A new PEGylated DIBMA variant called mPEG4-DIBMA = particularly promising: abolishes unspecific interactions with the tested peptide ligand and outperforms other polymers by achieving higher extraction efficiencies of MC4R from Sf9 insect cell membranes.

 

Methods

Mesoscale simulation of biomembranes with FreeDTS.

Pezeshkian W, Ipsen JH.

Nat Commun. 2024 Jan 16;15(1):548.

doi: 10.1038/s41467-024-44819-w.

FreeDTS software = computational research on biomembranes at the mesoscale. membrane is represented by a dynamically triangulated surface equipped with vertex-based inclusions to integrate the effects of MPs.

Possible to simulate complex membranes at different conditions: framed membranes with constant tension, vesicles and high-genus membranes with various fixed volumes or constant pressure differences and applying external forces to membrane regions possible to turn off the shape evolution of the membrane and focus solely on the organization of proteins.

=> ex: realistic membrane shapes obtained cryoET and backmap them into a finer simulation model.

=> simulation of realistic biomembranes with molecular resolution.

 

The High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX), an ancillary tool for the macromolecular crystallography beamlines at the ESRF.

Carpentier P, van der Linden P, Mueller-Dieckmann C.

Acta Crystallogr D Struct Biol. 2024 Feb 1.

doi: 10.1107/S2059798323010707.

This article describes the High-Pressure Freezing Laboratory for Macromolecular Crystallography (HPMX) at the ESRF: lab dedicated to investigating interactions between macromolecules and gases in crystallo (high-pressure cells adapted for helium, argon, krypton, xenon, nitrogen, oxygen, carbon dioxide and methane).

=> detect and map the internal architecture of proteins (pockets, tunnels and channels) that allows the storage and diffusion of ligands or substrates/products + investigation of catalytic mechanisms of gas-employing enzymes.

 

Miscellaneous

Predicting multiple conformations via sequence clustering and AlphaFold2. Nature 625, 832–839 (2024).

Wayment-Steele, H.K., Ojoawo, A., Otten, R. et al.

https://doi-org.insb.bib.cnrs.fr/10.1038/s41586-023-06832-9

 

AF-Cluster = a method to accurately predict conformational states of proteins without prior knowledge, allowing prediction of previously unknown conformational states. Method used here to predict the states of KaiB, RfaH and Mad2, three model metamorphic proteins (proteins that occupy more than one secondary structure) known to undergo fold-switching as a part of their biological function.

 

Establishing a synthetic orthogonal replication system enables accelerated evolution in E. coli.

Rongzhen Tian et al.

Science383,421-426(2024).

doiI:10.1126/science.adk1281

 

An Escherichia coli orthogonal replication system (EcORep) allows massively accelerated continuous evolution of introduced DNA in bacterial cells.

 

Origami fabric robot slithers like a snake

Nature 625, 635 (2024)

doi: https://doi-org.insb.bib.cnrs.fr/10.1038/d41586-024-00126-4

Design of a concertina-shaped robot to mimic linear motion that allows the reptiles to creep through tight spaces without shifting sideways. They used pieces of laminated fabric folded into segments.

 

Seven technologies to watch in 2024

Nature 625, 844-848 (2024)

doi: https://doi-org.insb.bib.cnrs.fr/10.1038/d41586-024-00173-x

 

Advances in artificial intelligence are at the heart of many of this year’s most exciting areas of technological innovation: Deep learning for protein design, deepfake detection, large-fragment DNA insertion, brain–computer interfaces, Super-duper resolution ( = expansion microscopy …sigh), cell atlases, nanomaterials printed in 3D.

 

Nausea and vomiting in pregnancy linked to hormone from fetus

Nature 625, 670-671 (2024)

doi: https://doi-org.insb.bib.cnrs.fr/10.1038/d41586-023-03940-4

Maternal sensitivity to a hormone produced by the fetus might underlie the risk of severe nausea and vomiting in human pregnancy — a finding that could open up strategies for the treatment of this debilitating condition.

 

How plants iron out the competing interests of growth and defence

Nature 625, 671-672 (2024)

doi: https://doi-org.insb.bib.cnrs.fr/10.1038/d41586-023-03995-3

Once a plant recognizes a pathogen, part of its defence strategy is to withhold iron. The mechanism involves suppression of root acquisition of iron by degrading a molecule that activates the iron-uptake pathway.

related article:

Cao, M., Platre, M.P., Tsai, HH. et al. Spatial IMA1 regulation restricts root iron acquisition on MAMP perception. Nature 625, 750–759 (2024). https://doi-org.insb.bib.cnrs.fr/10.1038/s41586-023-06891-y

 

Academic governances define rules and guidelines regarding our publishing activities and caution towards predatory journals:

 

https://sante.sorbonne-universite.fr/recherche/liste-des-revues-presumees-non-predatrices

 

https://www.cnrs.fr/fr/cnrsinfo/acces-ouvert-les-pratiques-des-scientifiques-analysees

 

A super cool video on Nanobody® (now patented by Sanofi), with shoutout to Alain Roussel and colleagues from AFMB Marseille:

https://www.arte.tv/fr/videos/104392-000-A/un-remede-de-chameau-la-revolution-des-nanocorps/

 

Fancy equipments available at Université Paris Cité: