Nature Structural Biology
8, 427 - 432 (2001)
doi:10.1038/87588
Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchangeDirk Brehmer1, Stefan Rüdiger1, 2, Claudia S. Gässler1, Dagmar Klostermeier3, 4, Lars Packschies4, Jochen Reinstein4, Matthias P. Mayer1
& Bernd Bukau11
Institut für Biochemie und Molekularbiologie, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Str. 7, D-79104 Freiburg, Germany. 2
Cambridge Centre for Protein Engineering, MRC Centre, Hills Road, Cambridge CB2 2QH, UK. 3
The Scripps Research Institute, Department of Molecular Biology, MB-19, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. 4
Max-Planck-Institut für molekulare Physiologie, Abteilung physikalische Biochemie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.
Correspondence should be addressed to Bernd Bukau bukau@ruf.uni-freiburg.deThe Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.
|
