Structural Basis for the Cooperation of Hsp70 and Hsp110 Chaperones in Protein Folding

@article{citeulike:2968242, abstract = {Summary Protein folding by Hsp70 is tightly controlled by cochaperones, including J-domain proteins that trigger ATP hydrolysis and nucleotide exchange factors (NEFs) that remove ADP from Hsp70. Here we present the crystal structure of the yeast NEF Sse1p (Hsp110) in complex with the nucleotide-binding domain (NBD) of Hsp70. Hsp110 proteins are homologous to Hsp70s and consist of an NBD, a [beta] sandwich domain, and a three helix bundle domain (3HBD). In the complex, the NBD of Sse1p is ATP bound, and together with the 3HBD it embraces the NBD of Hsp70, inducing opening and the release of bound ADP from Hsp70. Mutations that abolish NEF activity are lethal, thus defining nucleotide exchange on Hsp70 as an essential function of Sse1p. Our data suggest that Sse1p does not employ the nucleotide-dependent allostery and peptide-binding mode of canonical Hsp70s, and that direct interactions of substrate with Sse1p may support Hsp70-assisted protein folding in a cooperative process.}, author = {Polier, Sigrun and Dragovic, Zdravko and Hartl, Ulrich F. and Bracher, Andreas }, citeulike-article-id = {2968242}, doi = {10.1016/j.cell.2008.05.022}, journal = {Cell}, keywords = {folding, structure}, month = {June}, number = {6}, pages = {1068--1079}, posted-at = {2008-07-07 04:17:04}, priority = {2}, title = {Structural Basis for the Cooperation of Hsp70 and Hsp110 Chaperones in Protein Folding}, url = {http://dx.doi.org/10.1016/j.cell.2008.05.022}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:2968242 L3 - citeulike-article-id:2968242 TI - Structural Basis for the Cooperation of Hsp70 and Hsp110 Chaperones in Protein Folding JF - Cell VL - 133 IS - 6 SP - 1068 EP - 1079 N2 - Summary Protein folding by Hsp70 is tightly controlled by cochaperones, including J-domain proteins that trigger ATP hydrolysis and nucleotide exchange factors (NEFs) that remove ADP from Hsp70. Here we present the crystal structure of the yeast NEF Sse1p (Hsp110) in complex with the nucleotide-binding domain (NBD) of Hsp70. Hsp110 proteins are homologous to Hsp70s and consist of an NBD, a [beta] sandwich domain, and a three helix bundle domain (3HBD). In the complex, the NBD of Sse1p is ATP bound, and together with the 3HBD it embraces the NBD of Hsp70, inducing opening and the release of bound ADP from Hsp70. Mutations that abolish NEF activity are lethal, thus defining nucleotide exchange on Hsp70 as an essential function of Sse1p. Our data suggest that Sse1p does not employ the nucleotide-dependent allostery and peptide-binding mode of canonical Hsp70s, and that direct interactions of substrate with Sse1p may support Hsp70-assisted protein folding in a cooperative process. KW - folding KW - structure AU - Polier, Sigrun AU - Dragovic, Zdravko AU - Hartl, Ulrich AU - Bracher, Andreas PY - 2008/06/13/ UR - http://dx.doi.org/10.1016/j.cell.2008.05.022 ER -