9z0e: Difference between revisions

Latest revision as of 09:33, 14 January 2026

Structure of disulfide-crosslinked S. cerevisiae Hrd1 dimer bound to one copy of Hrd3 in MSP1D1 nanodisc

Structural highlights

9z0e is a 3 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13]

References

↑ Bordallo J, Wolf DH. A RING-H2 finger motif is essential for the function of Der3/Hrd1 in endoplasmic reticulum associated protein degradation in the yeast Saccharomyces cerevisiae. FEBS Lett. 1999 Apr 9;448(2-3):244-8. PMID:10218484
↑ Plemper RK, Bordallo J, Deak PM, Taxis C, Hitt R, Wolf DH. Genetic interactions of Hrd3p and Der3p/Hrd1p with Sec61p suggest a retro-translocation complex mediating protein transport for ER degradation. J Cell Sci. 1999 Nov;112 ( Pt 22):4123-34. PMID:10547371
↑ Wilhovsky S, Gardner R, Hampton R. HRD gene dependence of endoplasmic reticulum-associated degradation. Mol Biol Cell. 2000 May;11(5):1697-708. PMID:10793145
↑ Gardner RG, Swarbrick GM, Bays NW, Cronin SR, Wilhovsky S, Seelig L, Kim C, Hampton RY. Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p. J Cell Biol. 2000 Oct 2;151(1):69-82. PMID:11018054
↑ Deak PM, Wolf DH. Membrane topology and function of Der3/Hrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation. J Biol Chem. 2001 Apr 6;276(14):10663-9. Epub 2001 Jan 3. PMID:11139575 doi:https://dx.doi.org/10.1074/jbc.M008608200
↑ Bays NW, Gardner RG, Seelig LP, Joazeiro CA, Hampton RY. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat Cell Biol. 2001 Jan;3(1):24-9. PMID:11146622 doi:10.1038/35050524
↑ Gardner RG, Shearer AG, Hampton RY. In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Mol Cell Biol. 2001 Jul;21(13):4276-91. PMID:11390656 doi:10.1128/MCB.21.13.4276-4291.2001
↑ Gauss R, Sommer T, Jarosch E. The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment. EMBO J. 2006 May 3;25(9):1827-35. Epub 2006 Apr 13. PMID:16619026 doi:https://dx.doi.org/10.1038/sj.emboj.7601088
↑ Carvalho P, Goder V, Rapoport TA. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006 Jul 28;126(2):361-73. PMID:16873066 doi:10.1016/j.cell.2006.05.043
↑ Horn SC, Hanna J, Hirsch C, Volkwein C, Schutz A, Heinemann U, Sommer T, Jarosch E. Usa1 functions as a scaffold of the HRD-ubiquitin ligase. Mol Cell. 2009 Dec 11;36(5):782-93. doi: 10.1016/j.molcel.2009.10.015. PMID:20005842 doi:https://dx.doi.org/10.1016/j.molcel.2009.10.015
↑ Carvalho P, Stanley AM, Rapoport TA. Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p. Cell. 2010 Nov 12;143(4):579-91. doi: 10.1016/j.cell.2010.10.028. PMID:21074049 doi:https://dx.doi.org/10.1016/j.cell.2010.10.028
↑ Hampton RY, Gardner RG, Rine J. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell. 1996 Dec;7(12):2029-44. PMID:8970163
↑ Bordallo J, Plemper RK, Finger A, Wolf DH. Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol Biol Cell. 1998 Jan;9(1):209-22. PMID:9437001

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Bordallo J, Wolf DH. A RING-H2 finger motif is essential for the function of Der3/Hrd1 in endoplasmic reticulum associated protein degradation in the yeast Saccharomyces cerevisiae. FEBS Lett. 1999 Apr 9;448(2-3):244-8. PMID:10218484

[2] Plemper RK, Bordallo J, Deak PM, Taxis C, Hitt R, Wolf DH. Genetic interactions of Hrd3p and Der3p/Hrd1p with Sec61p suggest a retro-translocation complex mediating protein transport for ER degradation. J Cell Sci. 1999 Nov;112 ( Pt 22):4123-34. PMID:10547371

[3] Wilhovsky S, Gardner R, Hampton R. HRD gene dependence of endoplasmic reticulum-associated degradation. Mol Biol Cell. 2000 May;11(5):1697-708. PMID:10793145

[4] Gardner RG, Swarbrick GM, Bays NW, Cronin SR, Wilhovsky S, Seelig L, Kim C, Hampton RY. Endoplasmic reticulum degradation requires lumen to cytosol signaling. Transmembrane control of Hrd1p by Hrd3p. J Cell Biol. 2000 Oct 2;151(1):69-82. PMID:11018054

[5] Deak PM, Wolf DH. Membrane topology and function of Der3/Hrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation. J Biol Chem. 2001 Apr 6;276(14):10663-9. Epub 2001 Jan 3. PMID:11139575 doi:https://dx.doi.org/10.1074/jbc.M008608200

[6] Bays NW, Gardner RG, Seelig LP, Joazeiro CA, Hampton RY. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation. Nat Cell Biol. 2001 Jan;3(1):24-9. PMID:11146622 doi:10.1038/35050524

[7] Gardner RG, Shearer AG, Hampton RY. In vivo action of the HRD ubiquitin ligase complex: mechanisms of endoplasmic reticulum quality control and sterol regulation. Mol Cell Biol. 2001 Jul;21(13):4276-91. PMID:11390656 doi:10.1128/MCB.21.13.4276-4291.2001

[8] Gauss R, Sommer T, Jarosch E. The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection and Cdc48p recruitment. EMBO J. 2006 May 3;25(9):1827-35. Epub 2006 Apr 13. PMID:16619026 doi:https://dx.doi.org/10.1038/sj.emboj.7601088

[9] Carvalho P, Goder V, Rapoport TA. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell. 2006 Jul 28;126(2):361-73. PMID:16873066 doi:10.1016/j.cell.2006.05.043

[10] Horn SC, Hanna J, Hirsch C, Volkwein C, Schutz A, Heinemann U, Sommer T, Jarosch E. Usa1 functions as a scaffold of the HRD-ubiquitin ligase. Mol Cell. 2009 Dec 11;36(5):782-93. doi: 10.1016/j.molcel.2009.10.015. PMID:20005842 doi:https://dx.doi.org/10.1016/j.molcel.2009.10.015

[11] Carvalho P, Stanley AM, Rapoport TA. Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p. Cell. 2010 Nov 12;143(4):579-91. doi: 10.1016/j.cell.2010.10.028. PMID:21074049 doi:https://dx.doi.org/10.1016/j.cell.2010.10.028

[12] Hampton RY, Gardner RG, Rine J. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell. 1996 Dec;7(12):2029-44. PMID:8970163

[13] Bordallo J, Plemper RK, Finger A, Wolf DH. Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins. Mol Biol Cell. 1998 Jan;9(1):209-22. PMID:9437001

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9z0e is ON HOLD
+==Structure of disulfide-crosslinked S. cerevisiae Hrd1 dimer bound to one copy of Hrd3 in MSP1D1 nanodisc==
+<StructureSection load='9z0e' size='340' side='right'caption='[[9z0e]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
-Authors: Pisa, R., Rapoport, T.A.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9z0e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9Z0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9Z0E FirstGlance]. <br>
-Description: Structure of disulfide-crosslinked S. cerevisiae Hrd1 dimer bound to one copy of Hrd3 in MSP1D1 nanodisc
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9z0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9z0e OCA], [https://pdbe.org/9z0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9z0e RCSB], [https://www.ebi.ac.uk/pdbsum/9z0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9z0e ProSAT]</span></td></tr>
-[[Category: Pisa, R]]
+</table>
-[[Category: Rapoport, T.A]]
+== Function ==
+[https://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>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Pisa R]]
+[[Category: Rapoport TA]]

9z0e: Difference between revisions

Latest revision as of 09:33, 14 January 2026

Structure of disulfide-crosslinked S. cerevisiae Hrd1 dimer bound to one copy of Hrd3 in MSP1D1 nanodisc

Structural highlights

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References

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