Back to Search
Start Over
Insights into the structural dynamics of the Hsp110–Hsp70 interaction reveal the mechanism for nucleotide exchange activity
- Source :
- Proceedings of the National Academy of Sciences. 105:16519-16524
- Publication Year :
- 2008
- Publisher :
- Proceedings of the National Academy of Sciences, 2008.
-
Abstract
- Hsp110 proteins are relatives of canonical Hsp70 chaperones and are expressed abundantly in the eukaryotic cytosol. Recently, it has become clear that Hsp110 proteins are essential nucleotide exchange factors (NEFs) for Hsp70 chaperones. Here, we report the architecture of the complex between the yeast Hsp110, Sse1, and its cognate Hsp70 partner, Ssa1, as revealed by hydrogen–deuterium exchange analysis and site-specific cross-linking. The two nucleotide-binding domains (NBDs) of Sse1 and Ssa1 are positioned to face each other and form extensive contacts between opposite lobes of their NBDs. A second contact with the periphery of the Ssa1 NBD lobe II is likely mediated via the protruding C-terminal α-helical subdomain of Sse1. To address the mechanism of catalyzed nucleotide exchange, we have compared the hydrogen exchange characteristics of the Ssa1 NBD in complex with either Sse1 or the yeast homologs of the NEFs HspBP1 and Bag-1. We find that Sse1 exploits a Bag-1-like mechanism to catalyze nucleotide release, which involves opening of the Ssa1 NBD by tilting lobe II. Thus, Hsp110 proteins use a unique binding mode to catalyze nucleotide release from Hsp70s by a functionally convergent mechanism.
- Subjects :
- Saccharomyces cerevisiae Proteins
Mitochondrial Membrane Transport Proteins
DNA-binding protein
Nucleotide exchange factor
Mitochondrial membrane transport protein
Heat shock protein
HSP70 Heat-Shock Proteins
Protein Interaction Domains and Motifs
Nucleotide
HSP110 Heat-Shock Proteins
Binding site
Heat-Shock Proteins
Adenosine Triphosphatases
chemistry.chemical_classification
Binding Sites
Multidisciplinary
biology
Nucleotides
Membrane transport protein
Deuterium Exchange Measurement
Membrane Transport Proteins
Biological Sciences
DNA-Binding Proteins
chemistry
Biochemistry
Chaperone (protein)
biology.protein
Biophysics
Molecular Chaperones
Transcription Factors
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....9e9f6a9054d0ebc6a867885700623800