1y8x

From Proteopedia

(Difference between revisions)

Revision as of 00:52, 11 September 2015

Structural basis for recruitment of Ubc12 by an E2-binding domain in NEDD8's E1

Structural highlights

1y8x is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	UBE2M, UBC12 (HUMAN), UBE1C, UBA3 (HUMAN)
Activity:	Ubiquitin--protein ligase, with EC number 6.3.2.19
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[UBC12_HUMAN] Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation.^[1] ^[2] [UBA3_HUMAN] Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.^[3] ^[4] ^[5]

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

E2 conjugating enzymes play a central role in ubiquitin and ubiquitin-like protein (ublp) transfer cascades: the E2 accepts the ublp from the E1 enzyme and then the E2 often interacts with an E3 enzyme to promote ublp transfer to the target. We report here the crystal structure of a complex between the C-terminal domain from NEDD8's heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8's E2 (Ubc12). The structure and associated mutational analyses reveal molecular details of Ubc12 recruitment by NEDD8's E1. Interestingly, the E1's Ubc12 binding domain resembles ubiquitin and recruits Ubc12 in a manner mimicking ubiquitin's interactions with ubiquitin binding domains. Structural comparison with E2-E3 complexes indicates that the E1 and E3 binding sites on Ubc12 may overlap and raises the possibility that crosstalk between E1 and E3 interacting with an E2 could influence the specificity and processivity of ublp transfer.

Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.,Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA Mol Cell. 2005 Feb 4;17(3):341-50. PMID:15694336^[6]

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

References

↑ Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999 Apr 23;274(17):12036-42. PMID:10207026
↑ Huang DT, Miller DW, Mathew R, Cassell R, Holton JM, Roussel MF, Schulman BA. A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8. Nat Struct Mol Biol. 2004 Oct;11(10):927-35. Epub 2004 Sep 7. PMID:15361859 doi:10.1038/nsmb826
↑ Gong L, Yeh ET. Identification of the activating and conjugating enzymes of the NEDD8 conjugation pathway. J Biol Chem. 1999 Apr 23;274(17):12036-42. PMID:10207026
↑ Osaka F, Kawasaki H, Aida N, Saeki M, Chiba T, Kawashima S, Tanaka K, Kato S. A new NEDD8-ligating system for cullin-4A. Genes Dev. 1998 Aug 1;12(15):2263-8. PMID:9694792
↑ Bohnsack RN, Haas AL. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J Biol Chem. 2003 Jul 18;278(29):26823-30. Epub 2003 May 10. PMID:12740388 doi:10.1074/jbc.M303177200
↑ Huang DT, Paydar A, Zhuang M, Waddell MB, Holton JM, Schulman BA. Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1. Mol Cell. 2005 Feb 4;17(3):341-50. PMID:15694336 doi:10.1016/j.molcel.2004.12.020

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/1y8x"

@@ Line 2: / Line 2: @@
 <StructureSection load='1y8x' size='340' side='right' caption='[[1y8x]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1y8x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y8X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1y8x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y8X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y8X FirstGlance]. <br>
 </td></tr><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">UBE2M, UBC12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBE1C, UBA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2M, UBC12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBE1C, UBA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin--protein_ligase Ubiquitin--protein ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.19 6.3.2.19] </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=1y8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y8x OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y8x RCSB], [http://www.ebi.ac.uk/pdbsum/1y8x 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=1y8x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y8x OCA], [http://pdbe.org/1y8x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y8x RCSB], [http://www.ebi.ac.uk/pdbsum/1y8x PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1y8x" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Ubiquitin--protein ligase]]
 [[Category: Holton, J M]]

1y8x

From Proteopedia

Revision as of 00:52, 11 September 2015

Structural basis for recruitment of Ubc12 by an E2-binding domain in NEDD8's E1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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