1tt5: Difference between revisions

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<StructureSection load='1tt5' size='340' side='right'caption='[[1tt5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1tt5' size='340' side='right'caption='[[1tt5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1tt5]] is a 6 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=1TT5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1TT5 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1tt5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TT5 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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://proteopedia.org/fgij/fg.htm?mol=1tt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tt5 OCA], [http://pdbe.org/1tt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tt5 RCSB], [http://www.ebi.ac.uk/pdbsum/1tt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tt5 ProSAT]</span></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=1tt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tt5 OCA], [https://pdbe.org/1tt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tt5 RCSB], [https://www.ebi.ac.uk/pdbsum/1tt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tt5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UBC12_HUMAN 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.<ref>PMID:10207026</ref> <ref>PMID:15361859</ref>
[https://www.uniprot.org/uniprot/ULA1_HUMAN ULA1_HUMAN] Regulatory 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. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.<ref>PMID:10207026</ref> <ref>PMID:10722740</ref> <ref>PMID:12740388</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tt5 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tt5 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitin-like proteins (UBLs) such as NEDD8 are transferred to their targets by distinct, parallel, multienzyme cascades that involve the sequential action of E1, E2 and E3 enzymes. How do enzymes within a particular UBL conjugation cascade interact with each other? We report here that the unique N-terminal sequence of NEDD8's E2, Ubc12, selectively recruits NEDD8's E1 to promote thioester formation between Ubc12 and NEDD8. A peptide corresponding to Ubc12's N terminus (Ubc12N26) specifically binds and inhibits NEDD8's E1, the heterodimeric APPBP1-UBA3 complex. The structure of APPBP1-UBA3- Ubc12N26 reveals conserved Ubc12 residues docking in a groove generated by loops conserved in UBA3s but not other E1s. These data explain why the Ubc12-UBA3 interaction is unique to the NEDD8 pathway. These studies define a novel mechanism for E1-E2 interaction and show how enzymes within a particular UBL conjugation cascade can be tethered together by unique protein-protein interactions emanating from their common structural scaffolds.
A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.,Huang DT, Miller DW, Mathew R, Cassell R, Holton JM, Roussel MF, Schulman BA Nat Struct Mol Biol. 2004 Oct;11(10):927-35. Epub 2004 Sep 7. PMID:15361859<ref>PMID:15361859</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1tt5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Ubiquitin activating enzyme|Ubiquitin activating enzyme]]
*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
*[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cassell, R]]
[[Category: Cassell R]]
[[Category: Holton, J M]]
[[Category: Holton JM]]
[[Category: Huang, D T]]
[[Category: Huang DT]]
[[Category: Mathew, R]]
[[Category: Mathew R]]
[[Category: Miller, D W]]
[[Category: Miller DW]]
[[Category: Roussel, M F]]
[[Category: Roussel MF]]
[[Category: Schulman, B A]]
[[Category: Schulman BA]]
[[Category: Cell cycle]]
[[Category: Ligase]]

Latest revision as of 11:41, 14 February 2024

Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8

Structural highlights

1tt5 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ULA1_HUMAN Regulatory 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. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation.[1] [2] [3]

Evolutionary Conservation

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

See Also

References

  1. ↑ 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
  2. ↑ Chen Y, McPhie DL, Hirschberg J, Neve RL. The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in neurons. J Biol Chem. 2000 Mar 24;275(12):8929-35. PMID:10722740
  3. ↑ 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

1tt5, resolution 2.60Å

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