title: Molecular basis for the unique role of the AAA+ chaperone ClpV in type VI protein secretion.
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.
authors: Zentrum für Molekulare Biologie Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
authors: Aleksandra
authors: A
authors: Pietrosiuk
authors: Esther D
authors: ED
authors: Lenherr
authors: Sebastian
authors: S
authors: Falk
authors: Gabriele
authors: G
authors: Bönemann
authors: Jürgen
authors: J
authors: Kopp
authors: Hanswalter
authors: H
authors: Zentgraf
authors: Irmgard
authors: I
authors: Sinning
authors: Axel
authors: A
authors: Mogk
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D058947:Bacterial Secretion Systems / Q000502:physiology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018832:Molecular Chaperones / Q000737:chemistry*; D055503:Protein Multimerization / Q000502:physiology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D058947:Bacterial Secretion Systems; D018832:Molecular Chaperones; D000251:Adenosine Triphosphatases