6vjz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
==CryoEM structure of Hrd1-Usa1/Der1/Hrd3 complex of the expected topology==
==CryoEM structure of Hrd1-Usa1/Der1/Hrd3 complex of the expected topology==
-
<StructureSection load='6vjz' size='340' side='right'caption='[[6vjz]]' scene=''>
+
<StructureSection load='6vjz' size='340' side='right'caption='[[6vjz]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VJZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VJZ FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[6vjz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VJZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VJZ FirstGlance]. <br>
-
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vjz OCA], [http://pdbe.org/6vjz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vjz RCSB], [http://www.ebi.ac.uk/pdbsum/6vjz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vjz ProSAT]</span></td></tr>
+
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DER1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), HRD1, DER3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), HRD3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824]), USA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</td></tr>
 +
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vjz OCA], [http://pdbe.org/6vjz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vjz RCSB], [http://www.ebi.ac.uk/pdbsum/6vjz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vjz ProSAT]</span></td></tr>
</table>
</table>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/USA1_YEAST USA1_YEAST]] Scaffold protein of the endoplasmic reticulum-associated degradation (ERAD) (also known as endoplasmic reticulum quality control, ERQC) pathway involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). Has multiple functions in ERAD including recruitment of DER1 to the HRD1 ubiquitin ligase, and regulation of HRD1 activity. Involved in oligomerization of HRD1, which is required for ERAD-L, and in HRD1 autoubiquitination and degradation.<ref>PMID:16873066</ref> <ref>PMID:19898607</ref> <ref>PMID:19940128</ref> <ref>PMID:20005842</ref> <ref>PMID:21074049</ref> [[http://www.uniprot.org/uniprot/DER1_YEAST DER1_YEAST]] Component of the endoplasmic reticulum-associated degradation (ERAD) pathway. Specifically required for the ERAD-L pathway which mediates the degradation of proteins with misfolded lumenal domains within the endoplasmic reticulum.<ref>PMID:16873066</ref> <ref>PMID:20005842</ref> <ref>PMID:23363603</ref> <ref>PMID:8631297</ref> [[http://www.uniprot.org/uniprot/HRD3_YEAST HRD3_YEAST]] Component of the endoplasmic reticulum quality control (ERQC) system involved in ubiquitin-dependent degradation of missfolded endoplasmic reticulum proteins. Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). ERAD-L substrates are ubiquitinated through HRD1 in conjunction with the E2 ubiquitin-conjugating enzymes UBC1 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome. ERAD-M substrates are processed by the same HRD1-HRD3 core complex, but only a subset of the other components is required for ERAD-M. Stabilizes the HRD1 ubiquitin-protein ligase. Has also a function in recruiting misfolded protein substrates.<ref>PMID:10218484</ref> <ref>PMID:10547371</ref> <ref>PMID:10793145</ref> <ref>PMID:11018054</ref> <ref>PMID:11390656</ref> <ref>PMID:16619026</ref> <ref>PMID:16845381</ref> <ref>PMID:16873065</ref> <ref>PMID:16873066</ref> <ref>PMID:8970163</ref> [[http://www.uniprot.org/uniprot/HRD1_YEAST HRD1_YEAST]] E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC1 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of endoplasmic reticulum proteins (ERQC), also called ER-associated degradation (ERAD). Component of the HRD1 ubiquitin ligase complex, which is part of the ERAD-L and ERAD-M pathways responsible for the rapid degradation of soluble lumenal and membrane proteins with misfolded lumenal domains (ERAD-L), or ER-membrane proteins with misfolded transmembrane domains (ERAD-M). ERAD-L substrates are ubiquitinated through HRD1 in conjunction with the E2 ubiquitin-conjugating enzymes UBC1 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome. ERAD-M substrates are processed by the same HRD1-HRD3 core complex, but only a subset of the other components is required for ERAD-M.<ref>PMID:10218484</ref> <ref>PMID:10547371</ref> <ref>PMID:10793145</ref> <ref>PMID:11018054</ref> <ref>PMID:11139575</ref> <ref>PMID:11146622</ref> <ref>PMID:11390656</ref> <ref>PMID:16619026</ref> <ref>PMID:16873066</ref> <ref>PMID:20005842</ref> <ref>PMID:21074049</ref> <ref>PMID:8970163</ref> <ref>PMID:9437001</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Misfolded luminal endoplasmic reticulum (ER) proteins undergo ER-associated degradation (ERAD-L): They are retrotranslocated into the cytosol, polyubiquitinated, and degraded by the proteasome. ERAD-L is mediated by the Hrd1 complex (composed of Hrd1, Hrd3, Der1, Usa1, and Yos9), but the mechanism of retrotranslocation remains mysterious. Here, we report a structure of the active Hrd1 complex, as determined by cryo-electron microscopy analysis of two subcomplexes. Hrd3 and Yos9 jointly create a luminal binding site that recognizes glycosylated substrates. Hrd1 and the rhomboid-like Der1 protein form two "half-channels" with cytosolic and luminal cavities, respectively, and lateral gates facing one another in a thinned membrane region. These structures, along with crosslinking and molecular dynamics simulation results, suggest how a polypeptide loop of an ERAD-L substrate moves through the ER membrane.
 +
 +
Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex.,Wu X, Siggel M, Ovchinnikov S, Mi W, Svetlov V, Nudler E, Liao M, Hummer G, Rapoport TA Science. 2020 Apr 24;368(6489). pii: 368/6489/eaaz2449. doi:, 10.1126/science.aaz2449. PMID:32327568<ref>PMID:32327568</ref>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 6vjz" style="background-color:#fffaf0;"></div>
 +
== References ==
 +
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Atcc 18824]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Rapoport TA]]
+
[[Category: RING-type E3 ubiquitin transferase]]
-
[[Category: Wu X]]
+
[[Category: Rapoport, T A]]
 +
[[Category: Wu, X]]
 +
[[Category: Erad]]
 +
[[Category: Protein degradation]]
 +
[[Category: Protein transport]]
 +
[[Category: Retro-translocation]]
 +
[[Category: Ubiquitination]]

Revision as of 06:40, 6 May 2020

CryoEM structure of Hrd1-Usa1/Der1/Hrd3 complex of the expected topology

PDB ID 6vjz

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vjz"
Personal tools