A Molecular Switch Controls Assembly of Bacterial Focal Adhesions

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 May 29

PMID 38809974

Authors

Bouchra Attia

Laetitia My

Jean Philippe Castaing

Celine Dinet

Hugo Le Guenno

Victoria Schmidt

Leon Espinosa

Vivek Anantharaman

L Aravind

Corinne Sebban-Kreuzer

Matthieu Nouailler

Olivier Bornet

Patrick Viollier

Latifa Elantak

Tam Mignot

Affiliations

Soon will be listed here.

Abstract

Cell motility universally relies on spatial regulation of focal adhesion complexes (FAs) connecting the substrate to cellular motors. In bacterial FAs, the Adventurous gliding motility machinery (Agl-Glt) assembles at the leading cell pole following a Mutual gliding-motility protein (MglA)-guanosine 5'-triphosphate (GTP) gradient along the cell axis. Here, we show that GltJ, a machinery membrane protein, contains cytosolic motifs binding MglA-GTP and AglZ and recruiting the MreB cytoskeleton to initiate movement toward the lagging cell pole. In addition, MglA-GTP binding triggers a conformational shift in an adjacent GltJ zinc-finger domain, facilitating MglB recruitment near the lagging pole. This prompts GTP hydrolysis by MglA, leading to complex disassembly. The GltJ switch thus serves as a sensor for the MglA-GTP gradient, controlling FA activity spatially.

Citing Articles

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References

Sri Krishna S, Majumdar I, Grishin N . Structural classification of zinc fingers: survey and summary. Nucleic Acids Res. 2003; 31(2):532-50. PMC: 140525. DOI: 10.1093/nar/gkg161. View

Yang J, Anishchenko I, Park H, Peng Z, Ovchinnikov S, Baker D . Improved protein structure prediction using predicted interresidue orientations. Proc Natl Acad Sci U S A. 2020; 117(3):1496-1503. PMC: 6983395. DOI: 10.1073/pnas.1914677117. View

Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O . Highly accurate protein structure prediction with AlphaFold. Nature. 2021; 596(7873):583-589. PMC: 8371605. DOI: 10.1038/s41586-021-03819-2. View

Kofler M, Freund C . The GYF domain. FEBS J. 2006; 273(2):245-56. DOI: 10.1111/j.1742-4658.2005.05078.x. View

Drozdetskiy A, Cole C, Procter J, Barton G . JPred4: a protein secondary structure prediction server. Nucleic Acids Res. 2015; 43(W1):W389-94. PMC: 4489285. DOI: 10.1093/nar/gkv332. View

Benson D, Cavanaugh M, Clark K, Karsch-Mizrachi I, Lipman D, Ostell J . GenBank. Nucleic Acids Res. 2012; 41(Database issue):D36-42. PMC: 3531190. DOI: 10.1093/nar/gks1195. View

Johnson L, Eddy S, Portugaly E . Hidden Markov model speed heuristic and iterative HMM search procedure. BMC Bioinformatics. 2010; 11:431. PMC: 2931519. DOI: 10.1186/1471-2105-11-431. View

Islam S, Jolivet N, Cuzin C, Belgrave A, My L, Fleuchot B . Unmasking of the von Willebrand A-domain surface adhesin CglB at bacterial focal adhesions mediates myxobacterial gliding motility. Sci Adv. 2023; 9(8):eabq0619. PMC: 9946355. DOI: 10.1126/sciadv.abq0619. View

Faure L, Fiche J, Espinosa L, Ducret A, Anantharaman V, Luciano J . The mechanism of force transmission at bacterial focal adhesion complexes. Nature. 2016; 539(7630):530-535. PMC: 5465867. DOI: 10.1038/nature20121. View

10.

Bustamante V, Martinez-Flores I, Vlamakis H, Zusman D . Analysis of the Frz signal transduction system of Myxococcus xanthus shows the importance of the conserved C-terminal region of the cytoplasmic chemoreceptor FrzCD in sensing signals. Mol Microbiol. 2004; 53(5):1501-13. DOI: 10.1111/j.1365-2958.2004.04221.x. View

11.

Hauser M, Steinegger M, Soding J . MMseqs software suite for fast and deep clustering and searching of large protein sequence sets. Bioinformatics. 2016; 32(9):1323-30. DOI: 10.1093/bioinformatics/btw006. View

12.

Leonardy S, Miertzschke M, Bulyha I, Sperling E, Wittinghofer A, Sogaard-Andersen L . Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP. EMBO J. 2010; 29(14):2276-89. PMC: 2910265. DOI: 10.1038/emboj.2010.114. View

13.

Sun M, Wartel M, Cascales E, Shaevitz J, Mignot T . Motor-driven intracellular transport powers bacterial gliding motility. Proc Natl Acad Sci U S A. 2011; 108(18):7559-64. PMC: 3088616. DOI: 10.1073/pnas.1101101108. View

14.

Wu B, Lukin J, Yee A, Lemak A, Semesi A, Ramelot T . Solution structure of ribosomal protein L40E, a unique C4 zinc finger protein encoded by archaeon Sulfolobus solfataricus. Protein Sci. 2008; 17(3):589-96. PMC: 2248308. DOI: 10.1110/ps.073273008. View

15.

Vranken W, Boucher W, Stevens T, Fogh R, Pajon A, Llinas M . The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins. 2005; 59(4):687-96. DOI: 10.1002/prot.20449. View

16.

Treuner-Lange A, Macia E, Guzzo M, Hot E, Faure L, Jakobczak B . The small G-protein MglA connects to the MreB actin cytoskeleton at bacterial focal adhesions. J Cell Biol. 2015; 210(2):243-56. PMC: 4508894. DOI: 10.1083/jcb.201412047. View

17.

Webby M, Williams-Jones D, Press C, Kleanthous C . Force-Generation by the Trans-Envelope Tol-Pal System. Front Microbiol. 2022; 13:852176. PMC: 8928145. DOI: 10.3389/fmicb.2022.852176. View

18.

Tomar A, Schlaepfer D . Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility. Curr Opin Cell Biol. 2009; 21(5):676-83. PMC: 2754589. DOI: 10.1016/j.ceb.2009.05.006. View

19.

Connolley L, Szczepaniak J, Kleanthous C, Murray S . The quantitative basis for the redistribution of immobile bacterial lipoproteins to division septa. PLoS Comput Biol. 2021; 17(12):e1009756. PMC: 8751993. DOI: 10.1371/journal.pcbi.1009756. View

20.

Neuhaus D . Zinc finger structure determination by NMR: Why zinc fingers can be a handful. Prog Nucl Magn Reson Spectrosc. 2022; 130-131:62-105. PMC: 7614390. DOI: 10.1016/j.pnmrs.2022.07.001. View