Hsp90 is regulated by a switch point in the C-terminal domain

AUTOR(ES)

Retzlaff, Marco

FONTE

Nature Publishing Group

RESUMO

Heat shock protein 90 (Hsp90) is an abundant, dimeric ATP-dependent molecular chaperone, and ATPase activity is essential for its in vivo functions. S-nitrosylation of a residue located in the carboxy-terminal domain has been shown to affect Hsp90 activity in vivo. To understand how variation of a specific amino acid far away from the amino-terminal ATP-binding site regulates Hsp90 functions, we mutated the corresponding residue and analysed yeast and human Hsp90 variants both in vivo and in vitro. Here, we show that this residue is a conserved, strong regulator of Hsp90 functions, including ATP hydrolysis and chaperone activity. Unexpectedly, the variants alter both the C-terminal and N-terminal association properties of Hsp90, and shift its conformational equilibrium within the ATPase cycle. Thus, S-nitrosylation of this residue allows the fast and efficient fine regulation of Hsp90.

Documentos Relacionados

• Caracterização e interação do domínio C-terminal da chaperona Hsp90 humana e das co-chaperonas Tom 70 e Hop
• Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C-terminal region of murine HSP90 (HSP84).
• Src regulated by C-terminal phosphorylation is monomeric
• The activation function 2 domain of hepatic nuclear factor 4 is regulated by a short C-terminal proline-rich repressor domain.
• Rab-αGDI activity is regulated by a Hsp90 chaperone complex