1tt5

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(New page: 200px<br /> <applet load="1tt5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tt5, resolution 2.6&Aring;" /> '''Structure of APPBP1-...)
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[[Image:1tt5.gif|left|200px]]<br />
 
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<applet load="1tt5" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1tt5, resolution 2.6&Aring;" />
 
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'''Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8'''<br />
 
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==Overview==
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==Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8==
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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.
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<StructureSection load='1tt5' size='340' side='right'caption='[[1tt5]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</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>
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<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>
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<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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tt/1tt5_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1TT5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TT5 OCA].
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*[[3D structures of Ubiquitin activating enzyme|3D structures of Ubiquitin activating enzyme]]
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*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
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==Reference==
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== References ==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15361859 15361859]
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Cassell, R.]]
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[[Category: Cassell R]]
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[[Category: Holton, J.M.]]
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[[Category: Holton JM]]
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[[Category: Huang, D.T.]]
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[[Category: Huang DT]]
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[[Category: Mathew, R.]]
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[[Category: Mathew R]]
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[[Category: Miller, D.W.]]
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[[Category: Miller DW]]
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[[Category: Roussel, M.F.]]
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[[Category: Roussel MF]]
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[[Category: Schulman, B.A.]]
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[[Category: Schulman BA]]
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[[Category: ZN]]
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[[Category: cell cycle]]
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[[Category: ligase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:27:36 2007''
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Current revision

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

PDB ID 1tt5

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