Publication Date:
2013-02-09
Description:
HSP-100 protein machines, such as ClpB, play an essential role in reactivating protein aggregates that can otherwise be lethal to cells. Although the players involved are known, including the DnaK/DnaJ/GrpE chaperone system in bacteria, details of the molecular interactions are not well understood. Using methyl-transverse relaxation-optimized nuclear magnetic resonance spectroscopy, we present an atomic-resolution model for the ClpB-DnaK complex, which we verified by mutagenesis and functional assays. ClpB and GrpE compete for binding to the DnaK nucleotide binding domain, with GrpE binding inhibiting disaggregation. DnaK, in turn, plays a dual role in both disaggregation and subsequent refolding of polypeptide chains as they emerge from the aggregate. On the basis of a combined structural-biochemical analysis, we propose a model for the mechanism of protein aggregate reactivation by ClpB.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosenzweig, Rina -- Moradi, Shoeib -- Zarrine-Afsar, Arash -- Glover, John R -- Kay, Lewis E -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 Mar 1;339(6123):1080-3. doi: 10.1126/science.1233066. Epub 2013 Feb 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada. rina.rosenzweig@utoronto.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23393091" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphatases/*chemistry/genetics
;
Adenosine Triphosphate/chemistry/metabolism
;
Bacterial Proteins/chemistry
;
Heat-Shock Proteins/*chemistry/genetics
;
Hydrolysis
;
*Models, Chemical
;
Mutation
;
Nuclear Magnetic Resonance, Biomolecular
;
Protein Interaction Domains and Motifs
;
Protein Interaction Maps
;
Protein Multimerization
;
*Protein Refolding
;
Protein Structure, Tertiary
;
Protein Transport
;
Thermus thermophilus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
