The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and Hop is located in the dimerization domain of hsp90
The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and Hop is located in the dimerization domain of hsp90
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DOI：
10.1074/jbc.274.5.2682
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发表时间：
1999-01-29
影响因子：
4.8
通讯作者：
Ratajczak, T
中科院分区：
文献类型：
--
作者：
Carrello, A;Ingley, E;Ratajczak, T
类固醇受体相关免疫亲和素中结构相关的四肽重复基序和STI1同源物Hop介导与一个共同的细胞靶标HSP90的相互作用。我们用小鼠cDNA文库的双杂交系统筛选鉴定了HSP90中亲环素40(CyP40)的结合域。所有克隆均编码HSP90完整的羧基末端，并与小鼠HSP84的558-724位氨基酸对应的共同区域重叠，在体外证实了与细菌表达的CyP40和HSP90β的缺失突变体的相互作用，并进一步描绘了HSP90的124个残基-COOH末端片段，缺失了HSP90末端保守的MEEVD序列，排除了与CyP40的相互作用，表明该基序在HSP90功能中发挥了重要作用。我们发现CyP40和Hop与HSP90截断突变体的相互作用相似，并证明了Hop和FK506结合蛋白52与CyP40直接竞争结合到HSP90 COOH末端区域。我们的结果与HSP90离散的COOH末端结构域中Hop和类固醇受体相关免疫亲和素的共同四肽重复相互作用部位是一致的。HSP90的这个区域介导不依赖于ATP的伴侣活性，与HSP90的二聚化结构域重叠，并包括对类固醇受体相互作用重要的结构元件。
Structurally related tetratricopeptide repeat motifs in steroid receptor-associated immunophilins and the STI1 homolog, Hop, mediate the interaction with a common cellular target, hsp90, We have identified the binding domain in hsp90 for cyclophilin 40 (CyP40) using a two-hybrid system screen of a mouse cDNA library. All isolated clones encoded the intact carboxyl terminus of hsp90 and overlapped with a common region corresponding to amino acids 558-724 of murine hsp84, The interaction was confirmed in vitro with bacterially expressed CyP40 and deletion mutants of hsp90 beta and was delineated further to a 124-residue COOH-terminal segment of hsp90, Deletion of the conserved MEEVD sequence at the extreme carboxyl terminus of hsp90 precludes interaction with CyP40, signifying an important role for this motif in hsp90 function. We show that CyP40 and Hop display similar interaction profiles with hsp90 truncation mutants and present evidence for the direct competition of Hop and FK506-binding protein 52 with CyP40 for binding to the hsp90 COOH-terminal region. Our results are consistent with a common tetratricopeptide repeat interaction site for Hop and steroid receptor associated immunophilins within a discrete COOH-terminal domain of hsp90. This region of hsp90 mediates ATP-independent chaperone activity, overlaps the hsp90 dimerization domain, and includes structural elements important for steroid receptor interaction.