title: Dynamic nucleotide-dependent interactions of cysteine- and histidine-rich domain (CHORD)-containing Hsp90 cochaperones Chp-1 and melusin with cochaperones PP5 and Sgt1.
abstract: 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, Ca(2+), 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 Ca(2+). 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.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Hong
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Kim
authors.forename: Ah Ram
authors.initials: AR
authors.lastname: Wi
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: Miae
authors.initials: M
authors.lastname: Kang
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006023:Glycoproteins / Q000737:chemistry*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry; D028044:Phosphate-Binding Proteins; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C548819:CHORDC1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C478383:Chp-1 protein, mouse; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D018841:HSP90 Heat-Shock Proteins; C122158:Itgb1bp2 protein, mouse; D018832:Molecular Chaperones; D009124:Muscle Proteins; D009711:Nucleotides; D028044:Phosphate-Binding Proteins; C490164:SUGT1 protein, human; C530258:Sugt1 protein, mouse; C021240:tissue-factor-pathway inhibitor 2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002118:Calcium