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3dqv

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Revision as of 09:26, 14 November 2018

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation

Structural highlights

3dqv is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	NEDD8 (HUMAN), CUL5, VACM1 (HUMAN), RBX1, RNF75, ROC1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NEDD8_HUMAN] Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.^[1] ^[2] ^[3] [RBX1_HUMAN] E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair. The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.^[4] ^[5] ^[6] ^[7] ^[8] [CUL5_HUMAN] Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAk2. Seems to be involved poteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrangements in the crystal structure of NEDD8~Cul5(ctd)-Rbx1 and SAXS analysis of NEDD8~Cul1(ctd)-Rbx1 relative to their unmodified counterparts. In NEDD8ylated CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically reoriented, eliminating a CAND1-binding site and imparting multiple potential catalytic geometries to an associated E2. Biochemical analyses indicate that the structural malleability is important for both CRL NEDD8ylation and subsequent ubiquitination activities. Thus, our results point to a conformational control of CRL activity, with ligation of NEDD8 shifting equilibria to disfavor inactive CAND1-bound closed architectures, and favor dynamic, open forms that promote polyubiquitination.

Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation.,Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092^[9]

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

References

↑ Liakopoulos D, Busgen T, Brychzy A, Jentsch S, Pause A. Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5510-5. PMID:10318914
↑ Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, Kato S, Tanaka K. Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene. 1999 Nov 18;18(48):6829-34. PMID:10597293 doi:http://dx.doi.org/10.1038/sj.onc.1203093
↑ Amir RE, Iwai K, Ciechanover A. The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105. J Biol Chem. 2002 Jun 28;277(26):23253-9. Epub 2002 Apr 12. PMID:11953428 doi:http://dx.doi.org/10.1074/jbc.M200967200
↑ Kamura T, Conrad MN, Yan Q, Conaway RC, Conaway JW. The Rbx1 subunit of SCF and VHL E3 ubiquitin ligase activates Rub1 modification of cullins Cdc53 and Cul2. Genes Dev. 1999 Nov 15;13(22):2928-33. PMID:10579999
↑ Furukawa M, Zhang Y, McCarville J, Ohta T, Xiong Y. The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1. Mol Cell Biol. 2000 Nov;20(21):8185-97. PMID:11027288
↑ Groisman R, Kuraoka I, Chevallier O, Gaye N, Magnaldo T, Tanaka K, Kisselev AF, Harel-Bellan A, Nakatani Y. CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome. Genes Dev. 2006 Jun 1;20(11):1429-34. PMID:16751180 doi:http://dx.doi.org/10.1101/gad.378206
↑ Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y. Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell. 2006 May 5;22(3):383-94. PMID:16678110 doi:S1097-2765(06)00230-9
↑ Isobe T, Hattori T, Kitagawa K, Uchida C, Kotake Y, Kosugi I, Oda T, Kitagawa M. Adenovirus E1A inhibits SCF(Fbw7) ubiquitin ligase. J Biol Chem. 2009 Oct 9;284(41):27766-79. Epub 2009 Aug 13. PMID:19679664 doi:M109.006809
↑ Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell. 2008 Sep 19;134(6):995-1006. PMID:18805092 doi:http://dx.doi.org/10.1016/j.cell.2008.07.022

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3dqv"

@@ Line 1: / Line 1: @@
 ==Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation==
 <StructureSection load='3dqv' size='340' side='right' caption='[[3dqv]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEDD8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CUL5, VACM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RBX1, RNF75, ROC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3dqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqv OCA], [http://pdbe.org/3dqv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dqv RCSB], [http://www.ebi.ac.uk/pdbsum/3dqv PDBsum]</span></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=3dqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dqv OCA], [http://pdbe.org/3dqv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dqv RCSB], [http://www.ebi.ac.uk/pdbsum/3dqv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dqv ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dq/3dqv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dq/3dqv_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 45: / Line 46: @@
 [[Category: Schulman, B A]]
 [[Category: Scott, D C]]
+[[Category: Acetylation]]
 [[Category: Cullin]]
 [[Category: Cullin-ring ligase]]
+[[Category: Cytoplasm]]
 [[Category: Dna damage]]
 [[Category: Dna repair]]
@@ Line 58: / Line 61: @@
 [[Category: Signaling protein]]
 [[Category: Ubiquitin]]
+[[Category: Ubl conjugation]]
 [[Category: Ubl conjugation pathway]]
+[[Category: Zinc]]
 [[Category: Zinc-finger]]

3dqv

From Proteopedia

Revision as of 09:26, 14 November 2018

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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