作者: Steffen Preissler , Lukas Rohland , Yahui Yan , Ruming Chen , Randy J Read
DOI: 10.7554/ELIFE.29428
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摘要: The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP contributes to protein folding homeostasis by engaging unfolded client proteins in a process that is tightly coupled ATP binding and hydrolysis. inverse correlation between AMPylation the burden of ER suggests post-translational mechanism for adjusting BiP's activity changing levels stress, but underlying molecular details are unexplored. We present biochemical crystallographic studies indicating irrespective identity bound nucleotide biases towards conformation normally attained ATP-bound chaperone. does not affect interaction J-protein co-factors appears allosterically impair J protein-stimulated ATP-hydrolysis, resulting inability modified attain high affinity its substrates. These findings suggest which serves as switch inactivate BiP, limiting interactions with substrates whilst conserving ATP.