title: Specification of Hsp70 function by Type I and Type II Hsp40.
abstract: Cellular homeostasis and stress survival requires maintenance of the proteome and suppression of proteotoxicity. Molecular chaperones promote cell survival through repair of misfolded proteins and cooperation with protein degradation machines to discard terminally damaged proteins. Hsp70 family members play an essential role in cellular protein metabolism by binding and releasing nonnative proteins to facilitate protein folding, refolding and degradation. Hsp40 family members are Hsp70 co-chaperones that determine the fate of Hsp70 clients by facilitating protein folding, assembly, and degradation. Hsp40s select substrates for Hsp70 via use of an intrinsic chaperone activity to bind non-native regions of proteins. During delivery of bound cargo Hsp40s employ a conserved J-domain to stimulate Hsp70 ATPase activity and thereby stabilize complexes between Hsp70 and non-native proteins. Type I and Type II Hsp40s direct Hsp70 to preform multiple functions in protein homeostasis. This review describes the mechanisms by which Type I and Type II sub-types of Hsp40 bind and deliver substrates to Hsp70.
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina, 27599, Chapel Hill, NC, USA, dmcyr@med.unc.edu.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Cyr
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Ramos
mesh_terms: D000818:Animals; D002470:Cell Survival; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins