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Science 23 February 2001:
Vol. 291. no. 5508, pp. 1553 - 1557
DOI: 10.1126/science.1057268
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Reports

Structure of a Bag/Hsc70 Complex: Convergent Functional Evolution of Hsp70 Nucleotide Exchange Factors

Holger Sondermann,1 Clemens Scheufler,1 Christine Schneider,1 Jörg Höhfeld,2 F.-Ulrich Hartl,1 Ismail Moarefi1*

Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange.

1 Department of Cellular Biochemistry, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany.
2 Institut für Zellbiologie, Rheinische Friedrich- Wilhelms-Universität Bonn, D-53121 Bonn, Germany.
*   To whom correspondence should be addressed. E-mail: ismail{at}moarefi.com

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