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20240520_membrane digest

Membrane’s digest


Structural and molecular basis of choline uptake into the brain by FLVCR2.

Cater RJ, Mukherjee D, Gil-Iturbe E, Erramilli SK, Chen T, Koo K, Santander N, Reckers A, Kloss B, Gawda T, Choy BC, Zhang Z, Katewa A, Larpthaveesarp A, Huang EJ, Mooney SWJ, Clarke OB, Yee SW, Giacomini KM, Kossiakoff AA, Quick M, Arnold T, Mancia F.

Nature. 2024 May;629(8012):704-709.

doi: 10.1038/s41586-024-07326-y. Epub 2024 May 1.

PMID: 38693257.

Choline = essential nutrient (cell membrane synthesis, epigenetic modification and neurotransmission).

FLVCR1 (MFS transporter) = choline transporter not highly expressed at the blood-brain barrier / FLVCR2 expressed in endothelial cells at the blood-brain barrier.

Here: in vivo and in vitro demonstration that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain + cryoEM structures of choline-bound FLVCR2 in both IF and OF states.


Cleavage-independent activation of ancient eukaryotic gasdermins and structural mechanisms.

Li Y, Hou Y, Sun Q, Zeng H, Meng F, Tian X, He Q, Shao F, Ding J.

Science. 2024 May 17;384(6697):adm9190.

doi: 10.1126/science.adm9190. Epub 2024 May 17.

PMID: 38662913.

Gasdermins = proteins that mediate immune defense by triggering a type of cell death called pyroptosis. Gasdermins are usually activated by proteolytic cleavage that releases the active, membrane-perforating part of the protein. Here: discovery of two ancient types of gasdermins that work differently. One, from a basal metazoan, is switched on upon disruption of the chemical bonds linking an autoinhibited dimer. The other is from a fungus and is activated by pairing between incompatible strains to form membrane pores to kill mistakenly fused cells.



Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1.

Son Y, Kenny TC, Khan A, Birsoy K, Hite RK.

Nature. 2024 May;629(8012):710-716.

doi: 10.1038/s41586-024-07374-4. Epub 2024 May 1.

PMID: 38693265.

FLVCR1 = transporter responsible for the cellular uptake of choline and ethanolamine, essential precursors for PC and PE synthesis.

Here: structural studies => FLVCR1 binds both choline and ethanolamine at a common site but interacts differently with each metabolite.

Mutagenesis => distinct roles of FLVCR1 in transporting choline and ethanolamine.


Energetics of the Transmembrane Peptide Sorting by Hydrophobic Mismatch.

Fábián B, Javanainen M.

J Phys Chem Lett. 2024 May 13:5344-5349.

doi: 10.1021/acs.jpclett.4c00651. Epub ahead of print.

PMID: 38738950.

MD to study how peptides sort themselves along a membrane thickness gradient to resolve hydrophobic mismatch.

=> peptides tilt and diffuse to reduce mismatch at a rate proportional to the degree of mismatch.


Hydrophobic Mismatch in the Thylakoid Membrane Regulates Photosynthetic Light Harvesting.

Wilson S, Clarke CD, Carbajal MA, Buccafusca R, Fleck RA, Daskalakis V, Ruban AV.

J Am Chem Soc. 2024 May 17.

doi: 10.1021/jacs.4c05220. Epub ahead of print.

PMID: 38759103.

PsbS plays a crucial role in photoprotection mechanism by inducing hydrophobic mismatch in the thylakoid membrane, leading to membrane thinning and reversible clustering of LHCII.

This hydrophobic mismatch, influenced by dynamic lipid rearrangement and changes in the pKa of lumenal residues, facilitates the formation of photoprotective nanodomains, thereby regulating PSII function and protecting plants during photosynthesis.


Probing the energy barriers and stages of membrane protein unfolding using solid-state NMR spectroscopy.

Xiao P, Drewniak P, Dingwell DA, Brown LS, Ladizhansky V.

Sci Adv. 2024 May 17;10(20):eadm7907.

doi: 10.1126/sciadv.adm7907. Epub 2024 May 17.

PMID: 38758787.

ssNMR to study the thermally induced unfolding of human aquaporin 1.

=> unfolding occurs in a two-step process: first, a structured extracellular loop unfolds, followed by the TM domain unraveling as a single unit. This results in a misfolded state with high helical content but nonnative packing.

Role of loops in stabilizing MP structure + support the 3 stage model of MP folding.


Insights on the G protein-coupled receptor helix 8 solution structure and orientation using a neurotensin receptor 1 peptide.

Bower JB, Robson SA, Ziarek JJ.

Protein Sci. 2024 Jun;33(6):e4976.

doi: 10.1002/pro.4976.

PMID: 38757374.

Study of the structural stability and dynamics of the neurotensin receptor 1 (NTS1) H8 and C-terminal tail (Ctail) in membrane-mimicking environments.

=> zwitterionic phospholipids are effective in stabilizing the H8 structure / LMNG is not.

CD and NMR => sensitivity of the H8-Ctail region to membrane properties.


Helical reorganization in the context of membrane protein folding: Insights from simulations with bacteriorhodopsin (BR) fragments.

Chatterjee H, Mahapatra AJ, Zacharias M, Sengupta N.

Biochim Biophys Acta Biomembr. 2024 May 11;1866(5):184333.

doi: 10.1016/j.bbamem.2024.184333. Epub ahead of print.

PMID: 38740122.

Study of the folding process of BR, revealing that its C-terminal helix exhibits transient structural distortions that affect local membrane properties: N-terminal helix is more stable in the partially inserted state + full insertion stability arises from interactions between the N-terminal and C-terminal helices.


Concentration-Dependent Effects of Curcumin on Membrane Permeability and Structure.

Gudyka J, Ceja-Vega J, Ivanchenko K, Morocho Z, Panella M, Gamez Hernandez A, Clarke C, Perez E, Silverberg S, Lee S.

ACS Pharmacol Transl Sci. 2024 Apr 10;7(5):1546-1556.

doi: 10.1021/acsptsci.4c00093. PMID: 38751632.

Studied how curcumin interacts with membranes made from DOPC and DOPC with cholesterol.

=> curcumin has a concentration-dependent biphasic effect on water permeability.

Low concentrations: it decreases water permeability by binding to the lipid-water interface.

High concentrations: it increases permeability by inducing packing disorders in the membrane.

The presence of cholesterol generally reduces water permeability.


YdbH and YnbE form an intermembrane bridge to maintain lipid homeostasis in the outer membrane of Escherichia coli.

Kumar S, Davis RM, Ruiz N.

Proc Natl Acad Sci U S A. 2024 May 21;121(21):e2321512121.

doi: 10.1073/pnas.2321512121. Epub 2024 May 15.

PMID: 38748582.

Identification how PL are transported between E. coli IM and OM.

=> IM YdbH interacts with the OM lipoprotein YnbE to form a protein bridge, facilitating phospholipid transport (continuous hydrophobic β-groove to shield phospholipid acyl chains during transit).

In addition, YdbL (periplasmic) acts as a chaperone to prevent excessive multimerization of YnbE, ensuring proper bridge formation and function.


Stability of a biomembrane tube covered with proteins.

Janssen M, Liese S, Al-Izzi SC, Carlson A.

Phys Rev E. 2024 Apr;109(4-1):044403.

doi: 10.1103/PhysRevE.109.044403.

PMID: 38755805.

Membrane tubes = essential structural features in cells that facilitate biomaterial transport and inter- and intracellular signaling.

Here: study of the stability of a biomembrane tube coated with proteins by combining linear stability analysis, out-of-equilibrium hydrodynamic calculations, and numerical solutions of a Helfrich-like membrane model.

=> both long- and short-wavelength perturbations can destabilize the tubes. Interplay between membrane shape and protein density, where the shape instability concurs with a redistribution of proteins into a banded pattern.



Fluorescent Membrane Probes Obey the Israelachvili Rules

Felix Bayard, Stefan Matile, Helv. Chim. Acta 2024, e202400062.

Improved fluorescent membrane probes: combining palmitylation for hydrophobic interactions and glutamate dendrons for hydrophilic interactions, authors enhanced the solubility and performance of the probes in water and membranes.

These modifications adhere to the Israelachvili rules, ensuring the probes form stable micelles in water and effectively transfer into lipid bilayers.

=> new generation of fluorescent flipper probes with significantly improved brightness, responsiveness to membrane order, and stability compared to previous versions.


Development of a Fluorescent Ligand for the Intracellular Allosteric Binding Site of the Neurotensin Receptor 1.

Vogt H, Shinkwin P, Huber ME, Staffen N, Hübner H, Gmeiner P, Schiedel M, Weikert D.

ACS Pharmacol Transl Sci. 2024 Apr 18;7(5):1533-1545.

doi: 10.1021/acsptsci.4c00086.

PMID: 38751637.

Development of a fluorescent molecular probe based on an intracellular allosteric modulator for the neurotensin receptor subtype 1 (NTSR1).

NanoBRET-based ligand binding assays to explore the affinity and structure-activity relationships of allosteric NTSR1 modulators, aiding in the search for and optimization of novel allosteric ligands.

=> identification of novel chemotypes that bind to the intracellular allosteric pocket of NTSR1, which could serve as starting points for developing new intracellular allosteric ligands targeting NTSR1 for pain and addiction disorder therapy.



Generation and characterization of nanobodies targeting GPCR.

Zhang S, Fan Z, Liu J.

Biophys Rep. 2024 Feb 29;10(1):22-30.

doi: 10.52601/bpr.2023.230026.

PMID: 38737476.

Universal protocol to create Nb targeting GPCRs using cell membrane extracts from GPCR-overexpressing HEK293 cells for llama/alpaca immunization

=>Successful identification and characterization of these Nb through phage display bio-panning and recombinant expression in E. coli.


One-shot design elevates functional expression levels of a voltage-gated potassium channel.

Weinstein JJ, Saikia C, Karbat I, Goldenzweig A, Reuveny E, Fleishman SJ.

Protein Sci. 2024 Jun;33(6):e4995.

doi: 10.1002/pro.4995.

PMID: 38747377.

Automated design algorithm (called mPROSS) to improve the expression levels of MPs.

=> application to the Kv1.2-Kv2.1 paddle chimera voltage-gated potassium channel

=> successful design of 4 functional variants with increased whole-cell current densities in Xenopus oocytes.



Substrate uptake patterns shape niche separation in marine prokaryotic microbiome.

Zhao Z, Amano C, Reinthaler T, Orellana MV, Herndl GJ.

Sci Adv. 2024 May 17;10(20):eadn5143.

doi: 10.1126/sciadv.adn5143. Epub 2024 May 15.

PMID: 38748788.

Multi”omics” approach targeting ABC transporters and TBDTs to study substrate specificity: certain taxa primarily utilize ABC transporters to uptake organic nitrogenous compounds in the free-living fraction, while others utilize TBDTs for carbon-rich organic matter and metal chelates on particles.

Expression patterns of transporter proteins suggest distinct lifestyles of deep-sea prokaryotes.

=> Divergent use of transporters in organic matter assimilation reflects niche separation within prokaryote-mediated organic matter cycles in the marine environment.


Structural mechanism of bacteriophage lambda tail’s interaction with the bacterial receptor.

Ge X, Wang J.

Nat Commun. 2024 May 17;15(1):4185.

doi: 10.1038/s41467-024-48686-3. PMID: 38760367.

CryoEM structures of the bacteriophage lambda tail complexed with its receptor LamB from Shigella sonnei, as well as the closed central tail fiber.

=> the complex processes involved in bacteriophage infection initiation: interaction between lambda and its receptor LamB + conformational changes in the lambda tail tip upon LamB binding.




Unnatural Amino Acids for Biological Spectroscopy and Microscopy.

Feng RR, Wang M, Zhang W, Gai F.

Chem Rev. 2024 May 9.

doi: 10.1021/acs.chemrev.3c00944. Epub ahead of print.

PMID: 38722769.

Review of the advancements in the development and use of unnatural amino acids (UAAs) with specific spectroscopic characteristics in biological applications: vibrational, fluorescence, electron paramagnetic resonance (EPR), or nuclear magnetic resonance (NMR) probes.


World’s brightest X-rays: China first in Asia to build next-generation synchrotron.

Conroy G.

Nature. 2024 May 13.

doi: 10.1038/d41586-024-01346-4. Epub ahead of print.

PMID: 38736013.

The US$665-million High Energy Photon Source (HEPS) outside Beijing puts China among only a handful of countries that have fourth-generation synchrotron light sources.


Is the Internet bad for you? Huge study reveals surprise effect on well-being.

Wong C.

Nature. 2024 May 12.

doi: 10.1038/d41586-024-01410-z. Epub ahead of print.

PMID: 38740913.

A survey of more than 2.4 million people finds that being online can have a positive effect on welfare.


France’s research mega-campus faces leadership crisis.

Casassus B.

Nature. 2024 May;629(8012):513-514.

doi: 10.1038/d41586-024-01319-7.

PMID: 38702578.

The contest to elect the next president of Paris-Saclay University has collapsed, reflecting wider issues at the giant research centre.


Engineering colloidal crystals molecule by molecule.

Li Z, Mao C.

Science. 2024 May 17;384(6697):741-742.

doi: 10.1126/science.adp4370. Epub 2024 May 16.

PMID: 38753803.

DNA origami engineered to self-assemble into colloidal crystals with unprecedented control and programmability.

=> new crystalline materials in optics, sensing, and separation applications.


Dazzling auroras are just a warm-up as more solar storms are likely, scientists say.

Witze A.

Nature. 2024 May 13.

doi: 10.1038/d41586-024-01432-7. Epub ahead of print.

PMID: 38740915.

[…] Scientists expect the current solar cycle to peak some time this year, owing to the number of sunspots they are observing. The biggest storms typically happen months to years after this official peak. Furthermore, as the solar cycle progresses, sunspots tend to appear closer to the Suns equator, increasing the chances of coronal mass ejections that will head directly for Earth rather than out into space […]