6jwi: Difference between revisions

Latest revision as of 05:22, 21 November 2024

Yeast Npl4 in complex with Lys48-linked diubiquitin

Structural highlights

6jwi is a 4 chain structure with sequence from Mus musculus and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.55Å
Ligands:	BCN, GLC, MSE, ZN
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]

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^[8]

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:https://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:https://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:https://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
↑ 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:https://dx.doi.org/10.1038/s41467-019-13697-y

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1091/mbc.12.12.4114

[3] 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:https://dx.doi.org/10.1038/414652a

[4] 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

[5] 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

[6] 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:https://dx.doi.org/10.1016/j.molcel.2010.10.021

[7] 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

[8] 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:https://dx.doi.org/10.1038/s41467-019-13697-y

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6jwi is ON HOLD
+==Yeast Npl4 in complex with Lys48-linked diubiquitin==
+<StructureSection load='6jwi' size='340' side='right'caption='[[6jwi]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6jwi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JWI 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]] 2.55&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BCN:BICINE'>BCN</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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'>[https://proteopedia.org/fgij/fg.htm?mol=6jwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jwi OCA], [https://pdbe.org/6jwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jwi RCSB], [https://www.ebi.ac.uk/pdbsum/6jwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jwi ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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>
+<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 6jwi" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[3D structures of ubiquitin|3D structures of ubiquitin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Fukai S]]
+[[Category: Sato Y]]

6jwi: Difference between revisions

Latest revision as of 05:22, 21 November 2024

Yeast Npl4 in complex with Lys48-linked diubiquitin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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