title: GrpE, Hsp110/Grp170, HspBP1/Sil1 and BAG domain proteins: nucleotide exchange factors for Hsp70 molecular chaperones.
abstract: Molecular chaperones of the Hsp70 family are key components of the cellular protein folding machinery. Substrate folding is accomplished by iterative cycles of ATP binding, hydrolysis and release. The ATPase activity of Hsp70 is regulated by two main classes of cochaperones: J-domain proteins stimulate ATPase hydrolysis by Hsp70, while nucleotide exchange factors (NEF) facilitate its conversion from the ADP-bound to the ATP-bound state, thus closing the chaperone folding cycle. Beginning with the discovery of the prototypical bacterial NEF GrpE, a large diversity of Hsp70 nucleotide exchange factors has been identified, connecting Hsp70 to a multitude of cellular processes in the eukaryotic cell. Here we review recent advances towards structure and function of nucleotide exchange factors from the Hsp110/Grp170, HspBP1/Sil1 and BAG domain protein families and discuss how these cochaperones connect protein folding with quality control and degradation pathways.
authors.affiliation: Dept. of Cellular Biochemistry, Max-Planck-Institute of Biochemistry, 82152, Martinsried, Germany, bracher@biochem.mpg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bracher
authors.forename: Jacob
authors.initials: J
authors.lastname: Verghese
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D050957:HSP110 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D059748:Proteolysis; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; C109172:GrpE-like 1 mitochondrial protein, vertebrate; D020662:Guanine Nucleotide Exchange Factors; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C116331:HSPBP1 protein, human; D018832:Molecular Chaperones; C418483:SIL1 protein, human; C098410:glucose-regulated protein 170