The C-Terminal BAG Domain of BAG5 Induces Conformational Changes of the Hsp70 Nucleotide-Binding Domain for ADP-ATP Exchange

被引：68

作者：

Arakawa, Akihiko ^{[1
,2
]}

Handa, Noriko ^{[2
]}

Ohsawa, Noboru ^{[2
]}

Shida, Meiri ^{[1
,2
]}

Kigawa, Takanori ^{[2
,3
]}

Hayashi, Fumiaki ^{[2
]}

Shirouzu, Mikako ^{[2
]}

Yokoyama, Shigeyuki ^{[1
,2
]}

机构：

[1] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan

[2] RIKEN, Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300045, Japan

[3] Tokyo Inst Technol, Midori Ku, Yokohama, Kanagawa 2268502, Japan

来源：

STRUCTURE | 2010年 / 18卷 / 03期

关键词：

CHAPERONE ACTIVITY; STRUCTURAL BASIS; MOLECULAR CHAPERONES; PROTEIN; FAMILY; HSP110; HSC70; PROGRAM; COCHAPERONE; REVEALS;

D O I：

10.1016/j.str.2010.01.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ADP-ATP exchange by the molecular chaperone Hsp70 is enhanced by several cochaperones. BAG5 consists of five BAG domains and associates with the nucleotide-binding domain (NBD) of Hsp70. The overexpression of BAG5 in the cytosol reportedly disturbs Hsp70-mediated protein refolding and induces Parkinson's disease. In the present study, we found that the fifth BAG domain (BD5) of BAG5 is responsible for the interaction between Hsp70 and BAG5. We also determined the crystal structures of the BD5.NBD complex. BD5 binding caused two different types of NBD conformational changes, which both disrupted the nucleotide-binding groove. In fact, BD5 reduced the affinity of the NBD for ADP. Moreover, BD5, as well as the full-length BAG5, accelerated Hsp70-mediated refolding in an in vitro assay. Therefore, BAG5 can function as the nucleotide exchange factor of Hsp70 for the enhancement of protein refolding.

引用

页码：309 / 319

页数：11