In vitro evidence that hsp90 contains two independent chaperone sites
In vitro evidence that hsp90 contains two independent chaperone sites
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DOI：
10.1016/s0014-5793(97)01363-x
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发表时间：
1997-11
期刊：
影响因子：
3.5
通讯作者：
Jason C. Young;C. Schneider;F. Hartl
中科院分区：
文献类型：
--
作者：
Jason C. Young;C. Schneider;F. Hartl
HSP90是一种丰富的结构性表达的应激蛋白和分子伴侣。在这里，我们将人类HSP90分成三个主要结构域，以确定HSP90与未折叠多肽结合的假定伴侣位点。令人惊讶的是，HSP90的N-末端和C-末端结构域都阻止变性多肽的聚集。N结构域的伴侣活性被格尔达那霉素抑制，格尔达那霉素是HSP90介导的蛋白质重折叠的特异性抑制剂。虽然这两个结构域都抑制蛋白质聚集，但只有C结构域与VSV G的抗原肽结合。基于这些结果，HSP90可能是第一个包含两个具有不同特异性的独立伴侣位点的伴侣。
Hsp90 is an abundant and constitutively expressed stress protein and molecular chaperone. Here we dissected human hsp90 into three major domains to identify the putative chaperone site at which hsp90 binds unfolded polypeptide. Surprisingly, both the N-terminal and the C-terminal domain of hsp90 prevent the aggregation of denatured polypeptides. The chaperone activity of the N-domain is inhibited by geldanamycin, a specific inhibitor of hsp90-mediated protein refolding. While both domains suppress protein aggregation, only the C-domain binds an antigenic peptide derived from VSV G. Based on these results, hsp90 may be the first chaperone to contain two independent chaperone sites with differential specificity.