Molecular basis for the unique role of the AAA+ chaperone ClpV in type VI protein secretion

• Verfasst von: Pietrosiuk, Aleksandra [VerfasserIn]
• Verfasst von: Lenherr, Esther D. [VerfasserIn]
• Verfasst von: Falk, Sebastian [VerfasserIn]
• Verfasst von: Bönemann, Gabriele [VerfasserIn]
• Verfasst von: Kopp, Jürgen [VerfasserIn]
• Verfasst von: Zentgraf, Hanswalter [VerfasserIn]
• Verfasst von: Sinning, Irmgard [VerfasserIn]
• Verfasst von: Mogk, Axel [VerfasserIn]
• Titel: Molecular basis for the unique role of the AAA+ chaperone ClpV in type VI protein secretion
• Verf.angabe: Aleksandra Pietrosiuk, Esther D. Lenherr, Sebastian Falk, Gabriele Bönemann, Jürgen Kopp, Hanswalter Zentgraf, Irmgard Sinning, and Axel Mogk
• E-Jahr: 2011
• Jahr: July 7, 2011
• Umfang: 12 S.
• Fussnoten: Im Titel ist "+" hochgestellt ; Gesehen am 14.12.2022
• Titel Quelle: Enthalten in: The journal of biological chemistry
• Ort Quelle: Bethesda, Md. : ASBMB Publications, 1905
• Jahr Quelle: 2011
• Band/Heft Quelle: 286(2011), 34, Seite 30010-30021
• ISSN Quelle: 1083-351X
• DOI: doi:10.1074/jbc.M111.253377
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adenosine Triphosphatases
• Sach-SW: Bacterial Secretion Systems
• Sach-SW: Binding Sites
• Sach-SW: Crystallography, X-Ray
• Sach-SW: Molecular Chaperones
• Sach-SW: Protein Multimerization
• Sach-SW: Protein Structure, Secondary
• Sach-SW: Protein Structure, Tertiary
• Sach-SW: Vibrio cholerae
• K10plus-PPN: 1827027096

Abstract

Ring-forming AAA(+) ATPases act in a plethora of cellular processes by remodeling macromolecules. The specificity of individual AAA(+) proteins is achieved by direct or adaptor-mediated association with substrates via distinct recognition domains. We investigated the molecular basis of substrate interaction for Vibrio cholerae ClpV, which disassembles tubular VipA/VipB complexes, an essential step of type VI protein secretion and bacterial virulence. We identified the ClpV recognition site within VipB, showed that productive ClpV-VipB interaction requires the oligomeric state of both proteins, solved the crystal structure of a ClpV N-domain-VipB peptide complex, and verified the interaction surface by mutant analysis. Our results show that the substrate is bound to a hydrophobic groove, which is formed by the addition of a single α-helix to the core N-domain. This helix is absent from homologous N-domains, explaining the unique substrate specificity of ClpV. A limited interaction surface between both proteins accounts for the dramatic increase in binding affinity upon ATP-driven ClpV hexamerization and VipA/VipB tubule assembly by coupling multiple weak interactions. This principle ensures ClpV selectivity toward the VipA/VipB macromolecular complex.