TY - JOUR
T1 - Unraveling the Mechanism of Protein Disaggregation Through a ClpB-DnaK Interaction
AU - Rosenzweig, Rina
AU - Moradi, Shoeib
AU - Zarrine-Afsar, Arash
AU - Glover, John R.
AU - Kay, Lewis E.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874393637&partnerID=8YFLogxK
U2 - 10.1126/science.1233066
DO - 10.1126/science.1233066
M3 - Article
SN - 0036-8075
VL - 339
SP - 1080
EP - 1083
JO - Science
JF - Science
IS - 6123
ER -