Broad yet high substrate specificity: the challenge of AAA+ proteins

• Published in: Journal of structural biology Vol. 146; no. 1; pp. 90 - 98
• Main Authors: Mogk, Axel, Dougan, David, Weibezahn, Jimena, Schlieker, Christian, Turgay, Kursad, Bukau, Bernd
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2004
• Subjects: AAA+ superfamily; Adaptor protein; Adaptor Proteins, Vesicular Transport - metabolism; Chaperone; Enzyme Activation; Nucleoside-Triphosphatase - chemistry; Nucleoside-Triphosphatase - metabolism; Protease; Protein Structure, Tertiary; Substrate Specificity; AAA+ superfamily; Adaptor protein; Protease; Chaperone; Substrate specificity
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2003.10.009

AAA+ proteins remodel target substrates in an ATP-dependent manner, an activity that is of central importance for a plethora of cellular processes. While sharing a similar hexameric structure AAA+ proteins must exhibit differences in substrate recognition to fulfil their diverse biological functions. Here we describe strategies of AAA+ proteins to ensure substrate specificity. AAA domains can directly mediate substrate recognition, however, in general extra domains, added to the core AAA domain, control substrate interaction. Such extra domains may either directly recognize substrates or serve as a platform for adaptor proteins, which transfer bound substrates to their AAA+ partner proteins. The positioning of adaptor proteins in substrate recognition can enable them to control the activity of their partner proteins by coupling AAA+ protein activation to substrate availability.