20240506_membrane digest – Membrane Protein Biochemistry Lab

Membrane’s digest

The molecular basis of sugar detection by an insect taste receptor.

Gomes JV, Singh-Bhagania S, Cenci M, Chacon Cordon C, Singh M, Butterwick JA.

Nature. 2024 May;629(8010):228-234.

doi: 10.1038/s41586-024-07255-w. Epub 2024 Mar 6.

PMID: 38447670.

Insects use ionotropic gustatory receptors to discriminate sugars.

Here: structures (+structure-guided mutagenesis and functional assays) of gustatory receptor from the silkworm Bombyx mori to gain insight into the molecular basis of sugar selectivity.

Chemical specificity = combination of receptor-ligand interactions and allosteric coupling (coarse receptor tuning derived from size and chemical characteristics of the pocket, whereas fine-tuning of receptor activation is achieved through the selective engagement of an allosteric pathway that regulates ion conduction).

Structural insights into vesicular monoamine storage and drug interactions.

Ye J, Chen H, Wang K, Wang Y, Ammerman A, Awasthi S, Xu J, Liu B, Li W.

Nature. 2024 May;629(8010):235-243.

doi: 10.1038/s41586-024-07290-7. Epub 2024 Mar 18.

PMID: 38499039.

Elucidation of the structural mechanisms of vesicular monoamine transporters (VMATs), crucial for neurotransmitter storage and release (cryoEM st of human VMAT1 in complex with various monoamines and drugs).

The Folding Pathway of ABC Transporter CFTR: Effective and Robust.

van der Sluijs P, Hoelen H, Schmidt A, Braakman I.

J Mol Biol. 2024 Apr 26:168591.

doi: 10.1016/j.jmb.2024.168591. Epub ahead of print.

PMID: 38677493.

Understanding the folding pathways of CFTR is crucial for addressing cystic fibrosis (= diseases caused by misfolding). Research on CFTR folding has led to the development of drugs that modulate misfolded proteins, offering hope for patients.

Here: review highlighting the modular and tolerant nature of CFTR folding, the impact of modulator drugs, and the potential for insights into the folding of other ABC transporters.

A monomeric structure of human TMEM63A protein.

Wu X, Shang T, Lü X, Luo D, Yang D.

Proteins. 2024 Jun;92(6):750-756.

doi: 10.1002/prot.26660. Epub 2024 Jan 13.

PMID: 38217391.

SP CryoEM structure of human TMEM63A in the presence of calcium => distinct monomeric architecture containing eleven TM helices.

Ion permeation pathway is located within the monomeric configuration and a nonprotein density resembling lipid is observed.

The Structural Features of MlaD Illuminate its Unique Ligand-Transporting Mechanism and Ancestry.

Dutta A, Kanaujia SP.

Protein J. 2024 Apr;43(2):298-315.

doi: 10.1007/s10930-023-10179-5. Epub 2024 Feb 12.

PMID: 38347327.

Elucidation of the molecular mechanism underlying phospholipid transport by the membrane-associated solute-binding protein MlaD in Gram-negative bacteria.

Crystal structures reveal a homo-hexameric ring formation of EcMlaD with a hydrophobic central channel, where the C-terminal α-helical domain plays a crucial role in determining the protein’s oligomeric state.

=> Proposed “asymmetric protomer movement”.

The tilting motion of the central core reveals the transport mechanism of the sarco/endoplasmic reticulum Ca²⁺-ATPase.

Ma R, Briggs JM.

Int J Biol Macromol. 2024 Apr 30:132000.

doi: 10.1016/j.ijbiomac.2024.132000. Epub ahead of print.

PMID: 38697445.

Novel mechanism underlying SERCA function, where ATP hydrolysis induces a significant tilting motion of the central core, facilitating Ca2+ transport. The tilting angle decreases dramatically during the E2 -> E1 transition, triggering the restart of the transport cycle. Additionally, repulsion between phosphorylated D351 and phosphate groups in ADP leads to ADP release from the SERCA1a headpiece, further contributing to the transport process.

Membrane

Enhanced structure/function of mTSPO translocator in lipid:surfactant mixed micelles.

Saade C, Pozza A, Bonneté F, Finet S, Lutz-Bueno V, Tully MD, Varela PF, Lacapère JJ, Combet S.

Biochimie. 2024 Apr 23:S0300-9084(24)00083-X.

doi: 10.1016/j.biochi.2024.04.008. Epub ahead of print.

PMID: 38663457.

Structural and functional properties of TSPO in different amphiphilic environments, aiming to find optimal solubilization conditions. By replacing SDS with mixed lipid:surfactant micelles, the protein’s α-helix content, interactions, and stability are enhanced, leading to a more extended protein/belt complex.

TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site.

Nadezhdin KD, Neuberger A, Khosrof LS, Talyzina IA, Khau J, Yelshanskaya MV, Sobolevsky AI.

Sci Adv. 2024 May 3;10(18):eadn2453.

doi: 10.1126/sciadv.adn2453. Epub 2024 May 1.

PMID: 38691614.

Cryo-EM structures revealing the mechanisms of activation and inactivation of WT human TRPV3 channels in response to tetrahydrocannabivarin (THCV) and 2-aminoethoxydiphenylborane (2-APB).

=> distinct allosteric pathways for TRPV3 activation by small-molecule agonists: THCV binds to the vanilloid site, while 2-APB binds to different sites, inducing similar pore opening and lipid dissociation.

The interplay between membrane viscosity and ligand-binding receptor kinetics in lipid bilayers.

Bernard, C., Carotenuto, A.R., Pugno, N.M. et al.

Meccanica (2024).

https://doi.org/10.1007/s11012-024-01779-1

Discussion of the significance of lipid rafts and proposition of a chemo-mechanical model of lipid bilayers, incorporating both fluidity and elasticity, to explain how proteins regulate membrane dynamics. By enriching the model with a strain-level dependent viscosity, it aims to understand how alterations in membrane fluidity affect the activity of raft domains and cell mechano-signaling.

Molecules

From bottom-up to cell surface proteomics: detergents or no detergents, that is the question.

Brough Z, Zhao Z, Duong van Hoa F.

Biochem Soc Trans. 2024 Apr 26:BST20231020.

doi: 10.1042/BST20231020. Epub ahead of print.

PMID: 38666604.

Importance of measuring MP expression levels for various biological and medical applications +discussion of the challenges posed by the hydrophobic nature of MPs in sample preparation and the paradox of detergent use, which facilitates protein processing but introduces contaminants.

This review also explores detergent removal methods (fundamentals, applications, merits, and limitations).

Methods

Structural proteomics of a bacterial mega membrane protein complex: FtsH-HflK-HflC.

Akkulak H, İnce HK, Goc G, Lebrilla CB, Kabasakal BV, Ozcan S.

Int J Biol Macromol. 2024 Apr 30;269(Pt 1):131923.

doi: 10.1016/j.ijbiomac.2024.131923. Epub ahead of print.

PMID: 38697437.

Cross-linking mass spectrometry (XL-MS) and various software tools to elucidate protein interactions within a MP complex containing FtsH, HflK, and HflC. Multiple software tools employed to process the MS data => new interactions not previously reported, a total of 37 inter-protein and 148 intra-protein cross-links within the complex.

Microbio

Streptomyces umbrella toxin particles block hyphal growth of competing species.

Zhao Q, Bertolli S, Park YJ, Tan Y, Cutler KJ, Srinivas P, Asfahl KL, Fonesca-García C, Gallagher LA, Li Y, Wang Y, Coleman-Derr D, DiMaio F, Zhang D, Peterson SB, Veesler D, Mougous JD.

Nature. 2024 May;629(8010):165-173.

doi: 10.1038/s41586-024-07298-z. Epub 2024 Apr 17.

PMID: 38632398.

Streptomyces bacteria produce not only small-molecule antibiotics but also antibacterial protein complexes called umbrella particles, featuring a polymorphic toxin protein. These umbrella particles, characterized by a distinct structure, inhibit the growth of select Streptomyces species, suggesting a role in inter-species competition. Furthermore, the presence of umbrella loci in numerous Actinobacteria species indicates a widespread function beyond Streptomyces in mediating bacterial competition.

and the related News and views :

Bacteria deploy umbrella toxins against their competitors.

Coulthurst SJ.

Nature. 2024 May;629(8010):48-49.

doi: 10.1038/d41586-024-01016-5.

PMID: 38632420.

Bacteria make protein toxins to compete with other bacteria in microbial communities. A study of a common soil bacterium has revealed a previously unknown type of antibacterial toxin that forms a striking umbrella-like structure.

A team of chaperones play to win in the bacterial periplasm.

Devlin T, Fleming KG.

Trends Biochem Sci. 2024 Apr 26:S0968-0004(24)00081-1.

doi: 10.1016/j.tibs.2024.03.015. Epub ahead of print.

PMID: 38677921.

Discussion of the essential role of periplasmic chaperones and proteases in ensuring the proper folding and maintenance of OMPs in Gram-negative bacteria. These proteins prevent off-pathway aggregation of unfolded OMP precursors (uOMPs) in the periplasm => bacteria’s survival and virulence.

Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.

Duffey M, Jumde RP, da Costa RMA, Ropponen HK, Blasco B, Piddock LJV.

ACS Infect Dis. 2024 Apr 25.

doi: 10.1021/acsinfecdis.4c00091. Epub ahead of print.

PMID: 38661541.

Despite efforts to develop efflux inhibitors to combat antibiotic resistance, challenges such as formulation issues, toxicity, and narrow spectrum of inhibition have hindered their clinical use.

Here: recent advancements in computational tools = hope for further research and development of more effective bacterial efflux inhibitors.

Miscellaneous

Do insects have an inner life? Animal consciousness needs a rethink.

Lenharo M. Nature. 2024 May;629(8010):14-15.

doi: 10.1038/d41586-024-01144-y.

PMID: 38653828.

A declaration signed by dozens of scientists says there is ‘a realistic possibility’ for elements of consciousness in reptiles, insects and molluscs.

Antibiotics overused in pandemic

Science

News at a glance

WHO => 75% of COVID-19 hospitalized patients received antibiotics, despite only 8% having bacterial coinfections that necessitate such treatment.

This overuse of antibiotics, based on caution rather than evidence of bacterial infection, risks exacerbating antibiotic resistance.

=> importance of more judicious antibiotic use, with plans to address this issue at a United Nations meeting in September, highlighting the ongoing challenge of combating antibiotic resistance.

Biocomposite thermoplastic polyurethanes containing evolved bacterial spores as living fillers to facilitate polymer disintegration.

Kim HS, Noh MH, White EM, Kandefer MV, Wright AF, Datta D, Lim HG, Smiggs E, Locklin JJ, Rahman MA, Feist AM, Pokorski JK.

Nat Commun. 2024 Apr 30;15(1):3338.

doi: 10.1038/s41467-024-47132-8.

PMID: 38688899.

Novel approach to fabricate advanced biocomposite materials by incorporating spores from polymer-degrading bacteria into thermoplastic polyurethane using high-temperature melt extrusion. Engineered bacteria with improved heat tolerance ensure high cell survivability during manufacturing.

These materials disintegrate in compost without requiring a microbe-rich environment and exhibit programmable functionality, making them suitable for scalable industrial processes.

Purple is the new green: biopigments and spectra of Earth-like purple worlds.

Lígia Fonseca Coelho, Lisa Kaltenegger, Stephen Zinder, William Philpot, Taylor L Price, Trinity L Hamilton.

Monthly Notices of the Royal Astronomical Society.

Volume 530, Issue 2, May 2024, Pages 1363–1368.

https://doi.org/10.1093/mnras/stae601

Oxygenic photosynthesis => modern green landscapes, bacteriochlorophyll-based anoxygenic phototrophs can also colour their habitats and could dominate a much wider range of environments on Earth-like exoplanets.

Here: characterization of the reflectance spectra of a collection of purple sulfur and purple non-sulfur bacteria from a variety of anoxic and oxic environments => models for Earth-like planets where purple bacteria dominate the surface + impact of their signatures on the reflectance spectra of terrestrial exoplanets.