Dynamic Nucleotide-dependent Interactions of Cysteine- and Histidine-rich Domain (CHORD)-containing Hsp90 Cochaperones Chp-1 and Melusin with Cochaperones PP5 and Sgt1

• Published in: The Journal of biological chemistry 2013-01, Vol.288 (1), p.215-222
• Main Authors: Hong, Tae-Joon, Kim, Sangkyu, Wi, Ah Ram, Lee, Peter, Kang, Miae, Jeong, Jae-Hoon, Hahn, Ji-Sook
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adenosine Diphosphate - chemistry; Adenosine Diphosphate - metabolism; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Animals; Calcium; Calcium - chemistry; Calcium - metabolism; Carrier Proteins - chemistry; Cell Cycle Proteins - chemistry; Cochaperone; Cytoskeletal Proteins - chemistry; Gene Expression Regulation; Genetic Vectors; Glycoproteins - chemistry; HSP90 Heat-Shock Proteins - metabolism; Humans; Mice; Molecular Chaperone; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Muscle Proteins - chemistry; Nucleotide; Nucleotides - chemistry; Phosphate-Binding Proteins; Protein Binding; Protein Folding; Protein Interaction Mapping - methods; Protein Structure and Folding; Protein/Protein Interactions
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.398636

Mammals have two cysteine- and histidine-rich domain (CHORD)-containing Hsp90 cochaperones, Chp-1 and melusin, which are homologs of plant Rar1. It has been shown previously that Rar1 CHORD directly interacts with ADP bound to the nucleotide pocket of Hsp90. Here, we report that ADP and ATP can bind to Hsp90 cochaperones Chp-1 and PP5, inducing their conformational changes. Furthermore, we demonstrate that Chp-1 and melusin can interact with cochaperones PP5 and Sgt1 and with each other in an ATP-dependent manner. Based on the known structure of the Rar1-Hsp90 complex, His-186 has been identified as an important residue of Chp-1 for ADP/ATP binding. His-186 is necessary for the nucleotide-dependent interaction of Chp-1 not only with Hsp90 but also with Sgt1. In addition, Ca2+, which is known to bind to melusin, enhances the interactions of melusin with Hsp90 and Sgt1. Furthermore, melusin acquires the ADP preference for Hsp90 binding in the presence of Ca2+. Our newly discovered nucleotide-dependent interactions between cochaperones might provide additional complexity to the dynamics of the Hsp90 chaperone system, also suggesting potential Hsp90-independent roles for these cochaperones. Background: Hsp90 cochaperones are regulating interactors of Hsp90, but interactions between themselves are not well known. Results: CHORD-containing Hsp90 cochaperones interact with cochaperones PP5 and Sgt1 in the presence of ATP. Conclusion: Conformational changes induced by ATP binding play an important role in the regulation of interactions between cochaperones. Significance: Interactions between cochaperones might have Hsp90-independent roles that are regulated by cellular ATP concentration.