Broad yet high substrate specificity: the challenge of AAA+ proteins
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Updated: Aug 25, 2026

Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase
Published on: November 23, 2016
Axel Mogk1, David Dougan, Jimena Weibezahn
1Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, Im Neuenheimer Feld 282, Heidelberg D-69120, Germany. a.mogk@zmbh.uni-heidelberg.de
Abstract:
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.
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