BiP mutants that are unable to interact with endoplasmic reticulum DnaJ proteins provide insights into interdomain interactions in BiP

@article{citeulike:2369053, abstract = {The heat shock protein (Hsp)70 family of molecular chaperones interacts with unfolded proteins through a C-terminal substrate-binding domain (SBD) that is controlled by nucleotide binding to the N-terminal domain. The ATPase cycle is regulated by cochaperones, including DnaJ proteins that accelerate ATP hydrolysis to stabilize the Hsp70substrate complex. We found that R197 in hamster BiP, which resides at the surface of the nucleotide-binding domain, is critical for both association with endoplasmic reticulum DnaJ proteins and interaction with the SBD. Decreasing the positive charge at this residue enhanced basal ATPase activity, destabilized interaction with the SBD, and reduced substrate release both in vitro and in vivo. Mutation of three glutamic acids in the SBD mimicked many of these effects. Our data provide insights into communications between the two domains and suggest a mechanism by which DnaJ proteins increase ATP hydrolysis. 10.1073/pnas.0702132105}, author = {Awad, Walid and Estrada, Isaac and Shen, Ying and Hendershot, Linda M. }, citeulike-article-id = {2369053}, doi = {10.1073/pnas.0702132105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {allostery, chaperone, experiment, stability}, month = {January}, number = {4}, pages = {1164--1169}, posted-at = {2008-02-13 09:24:53}, priority = {2}, title = {BiP mutants that are unable to interact with endoplasmic reticulum DnaJ proteins provide insights into interdomain interactions in BiP}, url = {http://dx.doi.org/10.1073/pnas.0702132105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2369053 L3 - citeulike-article-id:2369053 TI - BiP mutants that are unable to interact with endoplasmic reticulum DnaJ proteins provide insights into interdomain interactions in BiP JF - Proceedings of the National Academy of Sciences VL - 105 IS - 4 SP - 1164 EP - 1169 N2 - The heat shock protein (Hsp)70 family of molecular chaperones interacts with unfolded proteins through a C-terminal substrate-binding domain (SBD) that is controlled by nucleotide binding to the N-terminal domain. The ATPase cycle is regulated by cochaperones, including DnaJ proteins that accelerate ATP hydrolysis to stabilize the Hsp70substrate complex. We found that R197 in hamster BiP, which resides at the surface of the nucleotide-binding domain, is critical for both association with endoplasmic reticulum DnaJ proteins and interaction with the SBD. Decreasing the positive charge at this residue enhanced basal ATPase activity, destabilized interaction with the SBD, and reduced substrate release both in vitro and in vivo. Mutation of three glutamic acids in the SBD mimicked many of these effects. Our data provide insights into communications between the two domains and suggest a mechanism by which DnaJ proteins increase ATP hydrolysis. 10.1073/pnas.0702132105 KW - allostery KW - chaperone KW - experiment KW - stability AU - Awad, Walid AU - Estrada, Isaac AU - Shen, Ying AU - Hendershot, Linda PY - 2008/01/29/ UR - http://dx.doi.org/10.1073/pnas.0702132105 ER -