p23 and Aha1: Distinct Functions Promote Client Maturation

• Published in: Sub-cellular biochemistry Vol. 101; p. 159
• Main Authors: Biebl, Maximilian M, Buchner, Johannes
• Format: Journal Article
• Language: English
• Published: United States 2023
• Subjects: Adenosine Triphosphatases - chemistry; HSP90 Heat-Shock Proteins - chemistry; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Humans; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Protein Binding; Protein Folding; Hsp90; p23; Aha1; Hch1; Glucocorticoid receptor
• ISSN: 0306-0225
• DOI: 10.1007/978-3-031-14740-1_6

Hsp90 is a conserved molecular chaperone regulating the folding and activation of a diverse array of several hundreds of client proteins. The function of Hsp90 in client processing is fine-tuned by a cohort of co-chaperones that modulate client activation in a client-specific manner. They affect the Hsp90 ATPase activity and the recruitment of client proteins and can in addition affect chaperoning in an Hsp90-independent way. p23 and Aha1 are central Hsp90 co-chaperones that regulate Hsp90 in opposing ways. While p23 inhibits the Hsp90 ATPase and stabilizes a client-bound Hsp90 state, Aha1 accelerates ATP hydrolysis and competes with client binding to Hsp90. Even though both proteins have been intensively studied for decades, research of the last few years has revealed intriguing new aspects of these co-chaperones that expanded our perception of how they regulate client activation. Here, we review the progress in understanding p23 and Aha1 as promoters of client processing. We highlight the structures of Aha1 and p23, their interaction with Hsp90, and how their association with Hsp90 affects the conformational cycle of Hsp90 in the context of client maturation.