6eof: Difference between revisions
New page: '''Unreleased structure''' The entry 6eof is ON HOLD until Paper Publication Authors: Yan, Y., Preissler, S., Read, R.J., Ron, D. Description: Crystal structure of AMPylated GRP78 in A... |
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==Crystal structure of AMPylated GRP78 in ADP state== | |||
<StructureSection load='6eof' size='340' side='right'caption='[[6eof]], [[Resolution|resolution]] 1.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6eof]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cricetulus_griseus Cricetulus griseus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EOF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EOF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6eof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eof OCA], [https://pdbe.org/6eof PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eof RCSB], [https://www.ebi.ac.uk/pdbsum/6eof PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eof ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BIP_CRIGR BIP_CRIGR] Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:29198525). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (PubMed:29198525). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (PubMed:29198525). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:P11021][UniProtKB:P20029]<ref>PMID:29198525</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:29064368</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6eof" style="background-color:#fffaf0;"></div> | ||
[[Category: Preissler | |||
[[Category: Read | ==See Also== | ||
[[Category: Yan | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cricetulus griseus]] | |||
[[Category: Large Structures]] | |||
[[Category: Preissler S]] | |||
[[Category: Read RJ]] | |||
[[Category: Ron D]] | |||
[[Category: Yan Y]] | |||
Latest revision as of 08:11, 21 November 2024
Crystal structure of AMPylated GRP78 in ADP stateCrystal structure of AMPylated GRP78 in ADP state
Structural highlights
FunctionBIP_CRIGR Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:29198525). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (PubMed:29198525). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (PubMed:29198525). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating.[UniProtKB:P11021][UniProtKB:P20029][1] Publication Abstract from PubMedThe 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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