6jwi

From Proteopedia

(Difference between revisions)

Current revision

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:	, , ,
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: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
↑ 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 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Large Structures | Mus musculus | Saccharomyces cerevisiae S288C | Fukai S | Sato Y

@@ Line 5: / Line 5: @@
 <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=PRD_900006:trehalose'>PRD_900006</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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/RL40_MOUSE RL40_MOUSE] Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:19754430</ref>   Component of the 60S subunit of the ribosome.<ref>PMID:19754430</ref> <ref>PMID:36517592</ref>
+[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 ==

6jwi

From Proteopedia

Current revision

Yeast Npl4 in complex with Lys48-linked diubiquitin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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