6eoe | pdb_00006eoe

Crystal structure of AMPylated GRP78 with nucleotide

spinqualitylabelsall models 6eoe, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eoe is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, FLC, SO4 Related: 5o4p Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 to ATP binding and hydrolysis. The inverse correlation between AMPylation and the burden of unfolded ER proteins suggests a post-translational mechanism for adjusting BiP's activity to changing levels of ER stress, but the underlying molecular details are unexplored. We present biochemical and crystallographic studies indicating that irrespective of the identity of the bound nucleotide AMPylation biases BiP towards a conformation normally attained by the ATP-bound chaperone. AMPylation does not affect the interaction between BiP and J-protein co-factors but appears to allosterically impair J protein-stimulated ATP-hydrolysis, resulting in the inability of modified BiP to attain high affinity for its substrates. These findings suggest a molecular mechanism by which AMPylation serves as a switch to inactivate BiP, limiting its interactions with substrates whilst conserving ATP. AMPylation targets the rate-limiting step of BiP's ATPase cycle for its functional inactivation.,Preissler S, Rohland L, Yan Y, Chen R, Read RJ, Ron D Elife. 2017 Oct 24;6. pii: e29428. doi: 10.7554/eLife.29428. PMID:29064368 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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