Abstract
The many protein processing reactions of the ATP-hydrolyzing Hsp70s are regulated by J cochaperones, which contain J domains that stimulate Hsp70 ATPase activity and accessory domains that present protein substrates to Hsp70s. We report the structure of a J domain complexed with a J responsive portion of a mammalian Hsp70. The J domain activates ATPase activity by directing the linker that connects the Hsp70 nucleotide binding domain (NBD) and substrate binding domain (SBD) toward a hydrophobic patch on the NBD surface. Binding of the J domain to Hsp70 displaces the SBD from the NBD, which may allow the SBD flexibility to capture diverse substrates. Unlike prokaryotic Hsp70, the SBD and NBD of the mammalian chaperone interact in the ADP state. Thus, although both nucleotides and J cochaperones modulate Hsp70 NBD:linker and NBD:SBD interactions, the intrinsic persistence of those interactions differs in different Hsp70s and this may optimize their activities for different cellular roles.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 422-433 |
| Number of pages | 12 |
| Journal | Molecular Cell |
| Volume | 28 |
| Issue number | 3 |
| DOIs | |
| State | Published - Nov 9 2007 |
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Keywords
- PROTEINS
ASJC Scopus subject areas
- Molecular Biology
Cite this
Structural Basis of J Cochaperone Binding and Regulation of Hsp70. / Jiang, Jianwen; Maes, E. Guy; Taylor, Alexander B.; Wang, Liping; Hinck, Andrew P.; Lafer, Eileen M; Sousa, Rui J.
In: Molecular Cell, Vol. 28, No. 3, 09.11.2007, p. 422-433.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural Basis of J Cochaperone Binding and Regulation of Hsp70
AU - Jiang, Jianwen
AU - Maes, E. Guy
AU - Taylor, Alexander B.
AU - Wang, Liping
AU - Hinck, Andrew P.
AU - Lafer, Eileen M
AU - Sousa, Rui J
PY - 2007/11/9
Y1 - 2007/11/9
N2 - The many protein processing reactions of the ATP-hydrolyzing Hsp70s are regulated by J cochaperones, which contain J domains that stimulate Hsp70 ATPase activity and accessory domains that present protein substrates to Hsp70s. We report the structure of a J domain complexed with a J responsive portion of a mammalian Hsp70. The J domain activates ATPase activity by directing the linker that connects the Hsp70 nucleotide binding domain (NBD) and substrate binding domain (SBD) toward a hydrophobic patch on the NBD surface. Binding of the J domain to Hsp70 displaces the SBD from the NBD, which may allow the SBD flexibility to capture diverse substrates. Unlike prokaryotic Hsp70, the SBD and NBD of the mammalian chaperone interact in the ADP state. Thus, although both nucleotides and J cochaperones modulate Hsp70 NBD:linker and NBD:SBD interactions, the intrinsic persistence of those interactions differs in different Hsp70s and this may optimize their activities for different cellular roles.
AB - The many protein processing reactions of the ATP-hydrolyzing Hsp70s are regulated by J cochaperones, which contain J domains that stimulate Hsp70 ATPase activity and accessory domains that present protein substrates to Hsp70s. We report the structure of a J domain complexed with a J responsive portion of a mammalian Hsp70. The J domain activates ATPase activity by directing the linker that connects the Hsp70 nucleotide binding domain (NBD) and substrate binding domain (SBD) toward a hydrophobic patch on the NBD surface. Binding of the J domain to Hsp70 displaces the SBD from the NBD, which may allow the SBD flexibility to capture diverse substrates. Unlike prokaryotic Hsp70, the SBD and NBD of the mammalian chaperone interact in the ADP state. Thus, although both nucleotides and J cochaperones modulate Hsp70 NBD:linker and NBD:SBD interactions, the intrinsic persistence of those interactions differs in different Hsp70s and this may optimize their activities for different cellular roles.
KW - PROTEINS
UR - http://www.scopus.com/inward/record.url?scp=35649024724&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35649024724&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2007.08.022
DO - 10.1016/j.molcel.2007.08.022
M3 - Article
C2 - 17996706
AN - SCOPUS:35649024724
VL - 28
SP - 422
EP - 433
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 3
ER -