p23 and Aha1: Distinct Functions Promote Client Maturation.

Area of Science:

• Molecular biology
• Protein biochemistry
• Cellular stress response

Background:

• Heat shock protein 90 (Hsp90) is a crucial molecular chaperone essential for the folding and activation of numerous client proteins.
• Hsp90 function is modulated by co-chaperones, which fine-tune client protein processing in a client-specific manner.
• Co-chaperones influence Hsp90's ATPase activity, client recruitment, and can also mediate Hsp90-independent chaperoning.

Approach:

• This review synthesizes recent findings on the Hsp90 co-chaperones p23 and Aha1.
• It highlights structural information regarding Aha1 and p23 and their interactions with Hsp90.
• The review examines how these interactions impact Hsp90's conformational cycle during client maturation.

Key Points:

• p23 and Aha1 are central Hsp90 co-chaperones with opposing regulatory roles.
• p23 inhibits Hsp90 ATPase activity, stabilizing client-bound states.
• Aha1 accelerates ATP hydrolysis and competes with client binding, promoting Hsp90's catalytic cycle.

Conclusions:

• Recent research has unveiled novel mechanisms by which p23 and Aha1 regulate Hsp90 client processing.
• Understanding these co-chaperones' roles expands our perception of Hsp90-mediated protein maturation.
• Further investigation into Aha1 and p23 interactions with Hsp90 is key to deciphering chaperone-client dynamics.