Physics-based modeling provides predictive understanding of selectively promiscuous substrate binding by Hsp70 chaperones.

ABSTRACT: To help cells cope with protein misfolding and aggregation, Hsp70 molecular chaperones selectively bind a variety of sequences ("selective promiscuity"). Statistical analyses from substrate-derived peptide arrays reveal that DnaK, the E. coli Hsp70, binds to sequences containing three to five branched hydrophobic residues, although otherwise the specific amino acids can vary considerably. Several high-resolution structures of the substrate -binding domain (SBD) of DnaK bound to peptides reveal a highly conserved configuration of the bound substrate and further suggest that the substrate-binding cleft consists of five largely independent sites for interaction with five consecutive substrate residues. Importantly, both substrate backbone orientations (N- to C- and C- to N-) allow essentially

SUBMITTER: Nordquist EB 

PROVIDER: S-EPMC8604352 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature