title: Unique peptide substrate binding properties of 110-kDa heat-shock protein (Hsp110) determine its distinct chaperone activity.
abstract: The molecular chaperone 70-kDa heat-shock proteins (Hsp70s) play essential roles in maintaining protein homeostasis. Hsp110, an Hsp70 homolog, is highly efficient in preventing protein aggregation but lacks the hallmark folding activity seen in Hsp70s. To understand the mechanistic differences between these two chaperones, we first characterized the distinct peptide substrate binding properties of Hsp110s. In contrast to Hsp70s, Hsp110s prefer aromatic residues in their substrates, and the substrate binding and release exhibit remarkably fast kinetics. Sequence and structure comparison revealed significant differences in the two peptide-binding loops: the length and properties are switched. When we swapped these two loops in an Hsp70, the peptide binding properties of this mutant Hsp70 were converted to Hsp110-like, and more impressively, it functionally behaved like an Hsp110. Thus, the peptide substrate binding properties implemented in the peptide-binding loops may determine the chaperone activity differences between Hsp70s and Hsp110s.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Xu
authors.forename: Evans Boateng
authors.initials: EB
authors.lastname: Sarbeng
authors.forename: Christina
authors.initials: C
authors.lastname: Vorvis
authors.forename: Divya Prasanna
authors.initials: DP
authors.lastname: Kumar
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D050957:HSP110 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D050957:HSP110 Heat-Shock Proteins; D010455:Peptides