Identification of a binding site on Hsc70 for the immunosuppressant 15-deoxyspergualin
Identification of a binding site on Hsc70 for the immunosuppressant 15-deoxyspergualin
复制标题
DOI：
10.1006/bbrc.1998.9775
复制
发表时间：
1998-12-09
影响因子：
3.1
通讯作者：
Marquardt, H
中科院分区：
文献类型：
--
作者：
Nadler, SG;Dischino, DD;Marquardt, H
Hsc70是热休克蛋白70家族的组成部分，参与了包括蛋白质折叠和分子陪伴在内的许多生物活动。之前，我们已经证明免疫抑制剂15-脱氧果苷（DSG）特异性地与Hsc70和Hsp90家族蛋白相互作用。尽管Hsc70蛋白底物的确切结合位点尚不清楚，但最近的一项研究表明，末端c端4个氨基酸(EEVD650)-E-647在调节ATPase活性、底物结合以及与HDJ-1的相互作用中发挥作用。这四种氨基酸也在Hsp90的c端发现，可能参与类似的功能。在这项研究中，我们发现DSG特异性地结合到这个EEVD调节结构域。DSC：与Hsc70结合不影响其结合多肽的能力。这些结果表明，除了ATP结合域外，Hsc70上还有两个额外的底物结合域。DSG应该为理解EEVD基序在生物过程中的作用提供一个工具。(C) 1998学术出版社。
Hsc70, the constitutive form of the heat shock protein 70 family of proteins, is involved in a number of biological activities which include protein folding and molecular chaperoning. Previously, we had shown that the immunosuppressant 15-deoxyspergualin (DSG) specifically interacted with Hsc70, as well as the Hsp90 family of proteins. Although the exact binding site on Hsc70 for protein substrates is unknown, a recent study shows that the extreme C-terminal four amino acids (EEVD650)-E-647 play a role in regulating ATPase activity, substrate binding, and interaction with HDJ-1. These four amino acids are also found at the C-terminus of Hsp90 and may be involved in similar functions. In this study, we show that DSG binds specifically to this EEVD regulatory domain. Binding of DSC: to Hsc70 did not affect its ability to bind peptides. These results suggest that in addition to the ATP binding domain, there are two additional substrate binding domains on Hsc70. DSG should provide a tool for understanding the role of the EEVD motif in biological processes. (C) 1998 Academic Press.