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20240429_membrane digest

Membrane’s digest


X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX.

Petit-Hartlein I, Vermot A, Thepaut M, Humm AS, Dupeux F, Dupuy J, Chaptal V, Marquez JA, Smith SME, Fieschi F.

Elife. 2024 Apr 19;13:RP93759.

doi: 10.7554/eLife.93759.

PMID: 38640072.

Crystal structures of Streptococcus pneumoniae NOX full-length and dehydrogenase (DH) domain constructs => suggestion that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer.


Future opportunities in solute carrier structural biology.

Newstead S.

Nat Struct Mol Biol. 2024 Apr;31(4):587-590.

doi: 10.1038/s41594-024-01271-0. Epub 2024 Apr 18.

PMID: 38637662.

Review discussing current advances and the emerging opportunities to target and modulate Solute carriers (SLCs).


Membrane-embedded machines.

Nat Struct Mol Biol. 2024 Apr;31(4):579.

doi: 10.1038/s41594-024-01303-9.

PMID: 38637661.

NSMB special issue publishing papers covering advances in Membrane Proteins, multifaceted molecular machines.


Beneath the surface: endosomal GPCR signaling.

Flores-Espinoza E, Thomsen ARB.

Trends Biochem Sci. 2024 Apr 19:S0968-0004(24)00072-0.

doi: 10.1016/j.tibs.2024.03.006. Epub ahead of print.

PMID: 38643023.

Emerging evidence suggests that some GPCRs continue to activate G proteins after having been internalized into endosomes.

Here: review of the recently elucidated mechanistic basis underlying endosomal GPCR signaling => physiological implications and pharmacological targeting.


Structural basis of prostaglandin efflux by MRP4.

Pourmal S, Green E, Bajaj R, Chemmama IE, Knudsen GM, Gupta M, Sali A, Cheng Y, Craik CS, Kroetz DL, Stroud RM.

Nat Struct Mol Biol. 2024 Apr;31(4):621-632.

doi: 10.1038/s41594-023-01176-4. Epub 2024 Jan 12.

PMID: 38216659.

6 CryoEM structures of ND-reconstituted MRP4 at various stages throughout its transport cycle (PGE1, PGE2 and the sulfonated-sterol DHEA-S binding; outward-occluded, catalytically compromised MRP4 mutant bound to ATP-Mg2+).


Identification of the potassium-binding site in serotonin transporter.

Hellsberg E, Boytsov D, Chen Q, Niello M, Freissmuth M, Rudnick G, Zhang YW, Sandtner W, Forrest LR.

Proc Natl Acad Sci U S A. 2024 Apr 30;121(18):e2319384121.

doi: 10.1073/pnas.2319384121. Epub 2024 Apr 23.

PMID: 38652746.

The serotonin transporter (SERT) mediates the clearance of serotonin from the synaptic cleft, with the resetting of its conformation for substrate binding being a rate-limiting step.

Here: studies suggesting that intracellular K+ ions, via K+ antiport, accelerate this process by binding to the Na2 site of SERT, facilitating serotonin uptake.


Tobacco aquaporin NtAQP1 and human aquaporin hAQP1 contribute to single cell photosynthesis in Synechococcus.

Joseph FM, Kaldenhoff R.

Biol Cell. 2024 Apr 23:e2470003.

doi: 10.1111/boc.202470003. Epub ahead of print.

PMID: 38653736.

Investigation of the effects of aquaporins on unicellular photosynthetically active organisms, specifically cyanobacteria.

Membrane CO2 conductivity = rate limiting and CO2-porins reduce the respective membrane resistance. Besides the tobacco aquaporin NtAQP1 also the human hAQP1 most likely functions as CO2 diffusion facilitator in the photosynthesis assay.


Lipid-dependent conformational dynamics of bacterial ATP-binding cassette transporter Sav1866.

Asadian SA, Hettige J, Moradi M.

bioRxiv [Preprint]. 2024 Apr 20:2024.04.18.590185.

doi: 10.1101/2024.04.18.590185. PMID: 38659884.

Investigation of the MD conformational dynamics of  Sav1866 in different lipid environments => behaviors influenced by lipid compositions, with a rapid transition to an IF-occluded conformation in POPE environments and a channel-like behavior in DMPC environments.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Wang H, Ishchenko A, Skudlarek J, Shen P, Dzhekieva L, Painter RE, Chen YT, Bukhtiyarova M, Leithead A, Tracy R, Babaoglu K, Bahnck-Teets C, Buevich A, Cabalu TD, Labroli M, Lange H, Lei Y, Li W, Liu J, Mann PA, Meng T, Mitchell HJ, Mulhearn J, Scapin G, Sha D, Shaw AW, Si Q, Tong L, Wu C, Wu Z, Xiao JC, Xu M, Zhang LK, McKenney D, Miller RR, Black TA, Cooke A, Balibar CJ, Klein DJ, Raheem I, Walker SS.

Nat Microbiol. 2024 Apr 22.

doi: 10.1038/s41564-024-01667-0. Epub ahead of print.

PMID: 38649414.

Description of, inhibitors (cerastecins) of the A. baumannii transporter MsbA, an LOS  (lipopolysaccharide or lipooligosaccharide) flippase.

cryoEM + biochemical analysis => cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping.

A derivative with optimized potency and pharmacokinetic properties => efficacy in murine models of bloodstream or pulmonary A. baumannii infection.




Effects of stand-alone polar residue on membrane protein stability and structure.

Chang YC, Cao Z, Chen WT, Huang WC.

Biochim Biophys Acta Biomembr. 2024 Apr 21:184325.

doi: 10.1016/j.bbamem.2024.184325. Epub ahead of print.

PMID: 38653423.

Polar residues witin transmembrane domains play essential roles in structural interactions and protein functions. Mutating apolar residues to polar ones in BR => destabilization of the protein, but the resulting polar residues form hydrogen bonds that help them adapt to the hydrophobic environment.

=> membrane proteins can tolerate stand-alone polar residues without compromising their overall structure.


Evaluation of Lipids for the Study of Photosynthetic Membranes.

Kirchhoff H, Vance L.

Methods Mol Biol. 2024;2790:427-438.

doi: 10.1007/978-1-0716-3790-6_23. PMID: 38649585.

2D TLC and gas chromatography techniques presented for quantitative analysis of lipid classes and fatty acids in thylakoid membranes. In addition, lipid extraction methods from isolated thylakoid membranes and leaves + procedure for the derivatization of fatty acids to fatty acid methyl esters (FAME) are described.




Synthesis, Characterization, and Self-Assembling Properties of New Amphiphilic Dendrons Bearing Branched TRIS-Derived Oligomers as Polar Head Groups

Stéphane Desgranges, Valentin Lacanau, Françoise Bonneté, Marine Soulié, Frédéric Bihel, Damien Bourgeois, and Christiane Contino-Pépin


Synthesis and characterization of a new family of dendritic surfactants called DendriTAC (single- or double-tailed surfactants containing hydrophobic hydrocarbon or fluorocarbon chains grafted onto TRIS-derived oligomeric polar heads).

Structural parameters of the surfactant assemblies in solution assessed by SAXS and DLS => self-assembling properties of H/F-DendriTACs are in agreement with usual trends of surfactant assemblies.

Great structural versatility => highly tunable self-assembly morphologies that can be adapted to specific applications.



Transient theory for scanning electrochemical microscopy of biological membrane transport: uncovering membrane-permeant interactions.

Huang SH, Amemiya S.

Analyst. 2024 Apr 22.

doi: 10.1039/d4an00411f. Epub ahead of print.

PMID: 38647017.

Scanning electrochemical microscopy (SECM) = powerful method to quantitatively investigate the transport of molecules and ions across biological membranes (allows for the in situ and non-destructive imaging and measurement of high membrane permeability under simple steady-state conditions).


Here: theoretical proposition that SECM enables the quantitative investigation of membrane-permeant interactions by employing transient conditions based on a Langmuir-type isotherm.



Can Protein Structure Prediction Methods Capture Alternative Conformations of Membrane Transporters?

Xie T, Huang J.

J Chem Inf Model. 2024 Apr 22;64(8):3524-3536.

doi: 10.1021/acs.jcim.3c01936. Epub 2024 Apr 2.

PMID: 38564295.

Curation of a data set (IOMemP), consisting of  experimentally determined high-resolution structures with substantial conformational changes to investigate the performance of current protein structure prediction methods in alternative conformation prediction (e.g IF/OF).

=> There is preference for specific states across various protein prediction methods. Coevolution information in MSAs influences state preference.

=> AlphaFold, when excluding coevolution information, estimates similar energies between the experimental IF and OF conformations, indicating that the energy model learned by AlphaFold is not biased toward any particular state. 


Investigations of membrane protein interactions in cells using fluorescence microscopy.

Abouelkheir M, Roy T, Krzyscik MA, Özdemir E, Hristova K.

Curr Opin Struct Biol. 2024 Apr 21;86:102816.

doi: 10.1016/ Epub ahead of print.

PMID: 38648680.

Ability to probe interactions between proteins in membranes has greatly evolved to the introduction of new fluorescence techniques: spatial distribution of a membrane protein, its association state, and the thermodynamic stability of the oligomers in the native milieu.


Analysis and prediction of interactions between transmembrane and non-transmembrane proteins.

Lu C, Jiang J, Chen Q, Liu H, Ju X, Wang H.

BMC Genomics. 2024 Apr 24;25(Suppl 1):401.

doi: 10.1186/s12864-024-10251-z.

PMID: 38658824.


Comprehensive analysis and prediction of TMP-nonTMP interactions using bioinformatics methods and deep learning-based solely on their sequence.


Exploiting protein language models for the precise classification of ion channels and ion transporters.

Ghazikhani H, Butler G.

Proteins. 2024 Apr 24.

doi: 10.1002/prot.26694. Epub ahead of print.

PMID: 38656743.

TooT-PLM-ionCT = comprehensive framework that consolidates systems distinguishing ion channels (ICs) from MPs, segregating ion transporters (ITs) from MPs, and differentiating ICs from ITs.

TooT-PLM-ionCT employs a combination of traditional classifiers and deep learning models for nuanced protein classification => superior performance in identifying ITs from MPs and distinguishing ICs from ITs.

web server



Lanthanum-fluoride electrode-based methods to monitor fluoride transport in cells and reconstituted lipid vesicles.

Kang CY, An M, Stockbridge RB.

Methods Enzymol. 2024;696:43-63.

doi: 10.1016/bs.mie.2024.01.012. Epub 2024 Feb 9.

PMID: 38658088.

F export proteins (channels and transporters) contribute to cellular resistance against fluoride ion.

Review summarizing quantitative methods to measure fluoride transport across membranes using fluoride-specific lanthanum-fluoride electrodes (MPs purified and reconstituted into lipid vesicles, or  fluoride efflux into living microbial cells).


NMR methods to detect fluoride binding and transport by membrane proteins.

Zhang J, Li J, Wang Y, Shi C.

Methods Enzymol. 2024;696:25-42.

doi: 10.1016/bs.mie.2023.12.009. Epub 2024 Jan 3.

PMID: 38658082.

Review on solid-state and solution NMR experiments to detect fluoride binding and transport by fluoride channels (developments in MP sample preparation and ssNMR methodology, using 1H, 19F and 13C-detection schemes).



Computational approaches to investigate fluoride binding, selectivity and transport across the membrane.

Mills KR, Torabifard H.

Methods Enzymol. 2024;696:109-154.

doi: 10.1016/bs.mie.2024.01.006. Epub 2024 Jan 22.

PMID: 38658077.

MD (and computational electrophysiology) to understand bacterial fluoride exporters, focusing on the CLCF F-/H+ antiporter and the Fluc F- channel.



Lifecycle of a predatory bacterium vampirizing its prey through the cell envelope and S-layer.

Santin, Y.G., Sogues, A., Bourigault, Y., Remaut H.K., Laloux, G.

Nat Commun 15, 3590 (2024).

The predatory bacterium Bdellovibrio exovorus attaches to and feeds upon Caulobacter crescentus, proliferating through non-binary division and forming secure junctions between their OMs. Contrary to previous assumptions, the presence of Caulobacter’s S-layer does not prevent predation, challenging its perceived role as a protective structure against predators.


Exposure to imipenem at sub-minimum inhibitory concentration leads to altered expression of major outer membrane proteins in Acinetobacter baumannii.

Nayak S, Akshay SD, Deekshit VK, Raj JM, Maiti B.

J Appl Microbiol. 2024 Apr 23:lxae105.

doi: 10.1093/jambio/lxae105. Epub ahead of print.

PMID: 38653725.

Exploration of the possible involvement of porins and OMPs in developing carbapenem resistance due to differential expression : OMPs are differentially expressed on exposure to imipenem.

=> insights into the role of specific OMPs in antibiotic resistance in A. baumannii.



Structural basis of iron piracy by a prominent human gut symbiont

Augustinas Silale, Yung Li Soo, Hannah Mark, Arnaud Basle, Bert van den Berg

BioRxiv [preprint]. 2024 Apr 15:2024.04.15.589501

doi: 10.1101/2024.04.15.589501

Bacteroides thetaiotaomicron xenosiderophores utilization system (Xus) composed of 3 proteins: XusA (TBDT), XusB (lipoprotein that bind iron-loaded siderophores) and XusC (PepSY domain-containing inner membrane protein). Here: X-ray structure of XusB with and without enterobactin (beta-propeller) + cryoEM structure of XusA+XusB => suggests mechanism by which XusB lipoprotein binds siderophores and passes them on to the XusA TonB-dependent transporter for translocation across the outer membrane.



Ensuring a sustained workforce to combat antibiotic resistance in the 21st century: the critical need for training the next-gen of scientists at the pre-doctoral level.

Shafer WM, Conn GL.

Antimicrob Agents Chemother. 2024 Apr 19:e0024424.

doi: 10.1128/aac.00244-24. Epub ahead of print.

PMID: 38639492.

Antibiotics revolutionized the treatment of bacterial infection and enhanced modern healthcare. While the current global antibiotic resistance crisis is widely acknowledged, the need for a highly trained cohort of scientists to continue and expand efforts to combat this threat has received less attention.

Training of pre-doctoral students in the ATB resistance field is critical for future efforts in combating this crisis and urge development of training programs that focus on this need.


Genomic, functional, and metabolic enhancements in multidrug-resistant Enterobacter bugandensis facilitating its persistence and succession in the International Space Station.

Sengupta P, Muthamilselvi Sivabalan SK, Singh NK, Raman K, Venkateswaran K.

Microbiome. 2024 Mar 23;12(1):62.

doi: 10.1186/s40168-024-01777-1.

PMID: 38521963.

Enterobacter bugandensis strains found on the International Space Station !!!

Study reveals resistance mechanisms and genomic adaptations, which align them with the ESKAPE pathogen group known for antimicrobial resistance.

=> highlights the unique evolutionary trajectories and colonization patterns of E. bugandensis in space, shedding light on microbial ecosystem dynamics within the ISS and emphasizing the importance of preventive measures to safeguard astronaut health.


This water bottle purifies your drink with energy from your steps.

Nature. 2024 Apr;628(8009):693.

doi: 10.1038/d41586-024-01074-9.

PMID: 38637708.

Static electricity generated by the foot striking the ground can be captured to kill pathogens.


Pre- and postnatal noise directly impairs avian development, with fitness consequences.

Meillère A, Buchanan KL, Eastwood JR, Mariette MM.

Science. 2024 Apr 26;384(6694):475-480.

doi: 10.1126/science.ade5868. Epub 2024 Apr 25.

PMID: 38662819.

Noise pollution has detrimental effects on zebra finches, causing embryonic death during exposure and impairing nestling growth and physiology. Cumulative exposure to pre- and postnatal traffic noise leads to telomere shortening across life stages and decreases offspring production throughout adulthood, indicating that noise pollution has pervasive and long-term impacts on avian populations.