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Publication Abstract from PubMed

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 alpha-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.

Molecular basis for the unique role of the AAA+ chaperone ClpV in type VI protein secretion.,Pietrosiuk A, Lenherr ED, Falk S, Bonemann G, Kopp J, Zentgraf H, Sinning I, Mogk A J Biol Chem. 2011 Aug 26;286(34):30010-21. doi: 10.1074/jbc.M111.253377. Epub, 2011 Jul 5. PMID:21733841^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.