Structural basis of interdomain communication in the Hsc70 chaperone

Jianwen Jiang, Kondury Prasad, Eileen M Lafer, Rui J Sousa

Research output: Contribution to journalArticle

228 Citations (Scopus)

Abstract

Hsp70 family proteins are highly conserved chaperones involved in protein folding, degradation, targeting and translocation, and protein complex remodeling. They are comprised of an N-terminal nucleotide binding domain (NBD) and a C-terminal protein substrate binding domain (SBD). ATP binding to the NBD alters SBD conformation and substrate binding kinetics, but an understanding of the mechanism of interdomain communication has been hampered by the lack of a crystal structure of an intact chaperone. We report here the 2.6 Å structure of a functionally intact bovine Hsc70 (bHsc70) and a mutational analysis of the observed interdomain interface and the immediately adjacent interdomain linker. This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalMolecular Cell
Volume20
Issue number4
DOIs
StatePublished - Nov 23 2005

Fingerprint

Protein Transport
Nucleotides
Adenosine Triphosphate
Protein Folding
Proteolysis
Proteins
C-terminal binding protein

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Structural basis of interdomain communication in the Hsc70 chaperone. / Jiang, Jianwen; Prasad, Kondury; Lafer, Eileen M; Sousa, Rui J.

In: Molecular Cell, Vol. 20, No. 4, 23.11.2005, p. 513-524.

Research output: Contribution to journalArticle

Jiang, Jianwen ; Prasad, Kondury ; Lafer, Eileen M ; Sousa, Rui J. / Structural basis of interdomain communication in the Hsc70 chaperone. In: Molecular Cell. 2005 ; Vol. 20, No. 4. pp. 513-524.
@article{87a3c2685c88483d97d14c8e2331c24f,
title = "Structural basis of interdomain communication in the Hsc70 chaperone",
abstract = "Hsp70 family proteins are highly conserved chaperones involved in protein folding, degradation, targeting and translocation, and protein complex remodeling. They are comprised of an N-terminal nucleotide binding domain (NBD) and a C-terminal protein substrate binding domain (SBD). ATP binding to the NBD alters SBD conformation and substrate binding kinetics, but an understanding of the mechanism of interdomain communication has been hampered by the lack of a crystal structure of an intact chaperone. We report here the 2.6 {\AA} structure of a functionally intact bovine Hsc70 (bHsc70) and a mutational analysis of the observed interdomain interface and the immediately adjacent interdomain linker. This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds.",
author = "Jianwen Jiang and Kondury Prasad and Lafer, {Eileen M} and Sousa, {Rui J}",
year = "2005",
month = "11",
day = "23",
doi = "10.1016/j.molcel.2005.09.028",
language = "English (US)",
volume = "20",
pages = "513--524",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Structural basis of interdomain communication in the Hsc70 chaperone

AU - Jiang, Jianwen

AU - Prasad, Kondury

AU - Lafer, Eileen M

AU - Sousa, Rui J

PY - 2005/11/23

Y1 - 2005/11/23

N2 - Hsp70 family proteins are highly conserved chaperones involved in protein folding, degradation, targeting and translocation, and protein complex remodeling. They are comprised of an N-terminal nucleotide binding domain (NBD) and a C-terminal protein substrate binding domain (SBD). ATP binding to the NBD alters SBD conformation and substrate binding kinetics, but an understanding of the mechanism of interdomain communication has been hampered by the lack of a crystal structure of an intact chaperone. We report here the 2.6 Å structure of a functionally intact bovine Hsc70 (bHsc70) and a mutational analysis of the observed interdomain interface and the immediately adjacent interdomain linker. This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds.

AB - Hsp70 family proteins are highly conserved chaperones involved in protein folding, degradation, targeting and translocation, and protein complex remodeling. They are comprised of an N-terminal nucleotide binding domain (NBD) and a C-terminal protein substrate binding domain (SBD). ATP binding to the NBD alters SBD conformation and substrate binding kinetics, but an understanding of the mechanism of interdomain communication has been hampered by the lack of a crystal structure of an intact chaperone. We report here the 2.6 Å structure of a functionally intact bovine Hsc70 (bHsc70) and a mutational analysis of the observed interdomain interface and the immediately adjacent interdomain linker. This analysis identifies interdomain interactions critical for chaperone function and supports an allosteric mechanism in which the interdomain linker invades and disrupts the interdomain interface when ATP binds.

UR - http://www.scopus.com/inward/record.url?scp=27944436648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27944436648&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2005.09.028

DO - 10.1016/j.molcel.2005.09.028

M3 - Article

C2 - 16307916

AN - SCOPUS:27944436648

VL - 20

SP - 513

EP - 524

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 4

ER -