6jwj

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Revision as of 09:03, 25 December 2019

Npl4 in complex with Ufd1

Structural highlights

6jwj is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NPL4_YEAST] Involved in the import of nuclear-targeted proteins into the nucleus and the export of poly(A) RNA out of the nucleus (PubMed:8930904, PubMed:11733065). Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway (PubMed:11739805, PubMed:11740563, PubMed:11847109). Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11733065). Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109). Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972). Involved in spindle disassembly probably by promoting the degradation of spindle assemby factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] [UFD1_YEAST] Functions at a post-ubiquitation step in the ubiquitin fusion degradation (UFD) pathway. Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway. Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1. Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD.^[8] ^[9] ^[10] ^[11]

Publication Abstract from PubMed

Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48-UN complex and its assembly.

Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4.,Sato Y, Tsuchiya H, Yamagata A, Okatsu K, Tanaka K, Saeki Y, Fukai S Nat Commun. 2019 Dec 13;10(1):5708. doi: 10.1038/s41467-019-13697-y. PMID:31836717^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell. 2001 Nov 30;107(5):667-77. PMID:11733065
↑ Bays NW, Wilhovsky SK, Goradia A, Hodgkiss-Harlow K, Hampton RY. HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins. Mol Biol Cell. 2001 Dec;12(12):4114-28. doi: 10.1091/mbc.12.12.4114. PMID:11739805 doi:http://dx.doi.org/10.1091/mbc.12.12.4114
↑ Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. 2001 Dec 6;414(6864):652-6. PMID:11740563 doi:http://dx.doi.org/10.1038/414652a
↑ Braun S, Matuschewski K, Rape M, Thoms S, Jentsch S. Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates. EMBO J. 2002 Feb 15;21(4):615-21. PMID:11847109
↑ Cao K, Nakajima R, Meyer HH, Zheng Y. The AAA-ATPase Cdc48/p97 regulates spindle disassembly at the end of mitosis. Cell. 2003 Oct 31;115(3):355-67. PMID:14636562
↑ Heo JM, Livnat-Levanon N, Taylor EB, Jones KT, Dephoure N, Ring J, Xie J, Brodsky JL, Madeo F, Gygi SP, Ashrafi K, Glickman MH, Rutter J. A stress-responsive system for mitochondrial protein degradation. Mol Cell. 2010 Nov 12;40(3):465-80. doi: 10.1016/j.molcel.2010.10.021. PMID:21070972 doi:http://dx.doi.org/10.1016/j.molcel.2010.10.021
↑ DeHoratius C, Silver PA. Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene. Mol Biol Cell. 1996 Nov;7(11):1835-55. PMID:8930904
↑ Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell. 2001 Nov 30;107(5):667-77. PMID:11733065
↑ Ye Y, Meyer HH, Rapoport TA. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature. 2001 Dec 6;414(6864):652-6. PMID:11740563 doi:http://dx.doi.org/10.1038/414652a
↑ Braun S, Matuschewski K, Rape M, Thoms S, Jentsch S. Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates. EMBO J. 2002 Feb 15;21(4):615-21. PMID:11847109
↑ Park S, Isaacson R, Kim HT, Silver PA, Wagner G. Ufd1 exhibits the AAA-ATPase fold with two distinct ubiquitin interaction sites. Structure. 2005 Jul;13(7):995-1005. PMID:16004872 doi:10.1016/j.str.2005.04.013
↑ Sato Y, Tsuchiya H, Yamagata A, Okatsu K, Tanaka K, Saeki Y, Fukai S. Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4. Nat Commun. 2019 Dec 13;10(1):5708. doi: 10.1038/s41467-019-13697-y. PMID:31836717 doi:http://dx.doi.org/10.1038/s41467-019-13697-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

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OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6jwj"

Categories: Large Structures | Fukai, S | Sato, Y | Protein binding | Ubiquitin

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6jwj is ON HOLD  until Paper Publication
+==Npl4 in complex with Ufd1==
+<StructureSection load='6jwj' size='340' side='right'caption='[[6jwj]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6jwj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JWJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JWJ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jwj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jwj OCA], [http://pdbe.org/6jwj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jwj RCSB], [http://www.ebi.ac.uk/pdbsum/6jwj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jwj ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NPL4_YEAST NPL4_YEAST]] Involved in the import of nuclear-targeted proteins into the nucleus and the export of poly(A) RNA out of the nucleus (PubMed:8930904, PubMed:11733065). Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway (PubMed:11739805, PubMed:11740563, PubMed:11847109). Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11733065). Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109). Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972). Involved in spindle disassembly probably by promoting the degradation of spindle assemby factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562).<ref>PMID:11733065</ref> <ref>PMID:11739805</ref> <ref>PMID:11740563</ref> <ref>PMID:11847109</ref> <ref>PMID:14636562</ref> <ref>PMID:21070972</ref> <ref>PMID:8930904</ref>  [[http://www.uniprot.org/uniprot/UFD1_YEAST UFD1_YEAST]] Functions at a post-ubiquitation step in the ubiquitin fusion degradation (UFD) pathway. Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway. Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1. Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD.<ref>PMID:11733065</ref> <ref>PMID:11740563</ref> <ref>PMID:11847109</ref> <ref>PMID:16004872</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48-UN complex and its assembly.
-Authors:
+Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4.,Sato Y, Tsuchiya H, Yamagata A, Okatsu K, Tanaka K, Saeki Y, Fukai S Nat Commun. 2019 Dec 13;10(1):5708. doi: 10.1038/s41467-019-13697-y. PMID:31836717<ref>PMID:31836717</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6jwj" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Fukai, S]]
+[[Category: Sato, Y]]
+[[Category: Protein binding]]
+[[Category: Ubiquitin]]

6jwj

From Proteopedia

Revision as of 09:03, 25 December 2019

Npl4 in complex with Ufd1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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