3apq: Difference between revisions
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< | ==Crystal structure of J-Trx1 fragment of ERdj5== | ||
<StructureSection load='3apq' size='340' side='right'caption='[[3apq]], [[Resolution|resolution]] 1.84Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3apq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3APQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3APQ 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]] 1.84Å</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=3apq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3apq OCA], [https://pdbe.org/3apq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3apq RCSB], [https://www.ebi.ac.uk/pdbsum/3apq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3apq ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DJC10_MOUSE DJC10_MOUSE] Endoplasmic reticulum disulfide reductase involved both in the correct folding of proteins and degradation of misfolded proteins. Required for efficient folding of proteins in the endoplasmic reticulum by catalyzing the removal of non-native disulfide bonds formed during the folding of proteins, such as LDLR. Also involved in endoplasmic reticulum-associated degradation (ERAD) by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. Interaction with HSPA5 is required its activity, not for the disulfide reductase activity, but to facilitate the release of DNAJC10 from its substrate. Promotes apoptotic signaling pathway in response to endoplasmic reticulum stress.<ref>PMID:12411443</ref> <ref>PMID:12446677</ref> <ref>PMID:18653895</ref> <ref>PMID:21329881</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ER-associated degradation (ERAD) is an ER quality-control process that eliminates terminally misfolded proteins. ERdj5 was recently discovered to be a key ER-resident PDI family member protein that accelerates ERAD by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. We here solved the crystal structure of full-length ERdj5, thereby revealing that ERdj5 contains the N-terminal J domain and six tandem thioredoxin domains that can be divided into the N- and C-terminal clusters. Our systematic biochemical analyses indicated that two thioredoxin domains that constitute the C-terminal cluster form the highly reducing platform that interacts with EDEM1 and reduces EDEM1-recruited substrates, leading to their facilitated degradation. The pulse-chase experiment further provided direct evidence for the sequential movement of an ERAD substrate from calnexin to the downstream EDEM1-ERdj5 complex, and then to the retrotranslocation channel, probably through BiP. We present a detailed molecular view of how ERdj5 mediates ERAD in concert with EDEM1. | |||
Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.,Hagiwara M, Maegawa K, Suzuki M, Ushioda R, Araki K, Matsumoto Y, Hoseki J, Nagata K, Inaba K Mol Cell. 2011 Feb 18;41(4):432-44. PMID:21329881<ref>PMID:21329881</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3apq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DnaJ homolog 3D structures|DnaJ homolog 3D structures]] | |||
*[[ER-resident protein|ER-resident protein]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[ | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Inaba | [[Category: Inaba K]] | ||
[[Category: Nagata | [[Category: Nagata K]] | ||
[[Category: Suzuki | [[Category: Suzuki M]] | ||
Latest revision as of 18:51, 4 October 2023
Crystal structure of J-Trx1 fragment of ERdj5Crystal structure of J-Trx1 fragment of ERdj5
Structural highlights
FunctionDJC10_MOUSE Endoplasmic reticulum disulfide reductase involved both in the correct folding of proteins and degradation of misfolded proteins. Required for efficient folding of proteins in the endoplasmic reticulum by catalyzing the removal of non-native disulfide bonds formed during the folding of proteins, such as LDLR. Also involved in endoplasmic reticulum-associated degradation (ERAD) by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. Interaction with HSPA5 is required its activity, not for the disulfide reductase activity, but to facilitate the release of DNAJC10 from its substrate. Promotes apoptotic signaling pathway in response to endoplasmic reticulum stress.[1] [2] [3] [4] Publication Abstract from PubMedER-associated degradation (ERAD) is an ER quality-control process that eliminates terminally misfolded proteins. ERdj5 was recently discovered to be a key ER-resident PDI family member protein that accelerates ERAD by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. We here solved the crystal structure of full-length ERdj5, thereby revealing that ERdj5 contains the N-terminal J domain and six tandem thioredoxin domains that can be divided into the N- and C-terminal clusters. Our systematic biochemical analyses indicated that two thioredoxin domains that constitute the C-terminal cluster form the highly reducing platform that interacts with EDEM1 and reduces EDEM1-recruited substrates, leading to their facilitated degradation. The pulse-chase experiment further provided direct evidence for the sequential movement of an ERAD substrate from calnexin to the downstream EDEM1-ERdj5 complex, and then to the retrotranslocation channel, probably through BiP. We present a detailed molecular view of how ERdj5 mediates ERAD in concert with EDEM1. Structural basis of an ERAD pathway mediated by the ER-resident protein disulfide reductase ERdj5.,Hagiwara M, Maegawa K, Suzuki M, Ushioda R, Araki K, Matsumoto Y, Hoseki J, Nagata K, Inaba K Mol Cell. 2011 Feb 18;41(4):432-44. PMID:21329881[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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