|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5t53' size='340' side='right'caption='[[5t53]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5t53' size='340' side='right'caption='[[5t53]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t53]] is a 1 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=5T53 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T53 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t53]] is a 1 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=5T53 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T53 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <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]] 2.699Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESCO1, EFO1, KIAA1911 ([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=ACO:ACETYL+COENZYME+*A'>ACO</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t53 OCA], [http://pdbe.org/5t53 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t53 RCSB], [http://www.ebi.ac.uk/pdbsum/5t53 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t53 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=5t53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t53 OCA], [https://pdbe.org/5t53 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t53 RCSB], [https://www.ebi.ac.uk/pdbsum/5t53 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t53 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ESCO1_HUMAN ESCO1_HUMAN]] Acetyltransferase required for the establishment of sister chromatid cohesion and couple the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3.<ref>PMID:14576321</ref> <ref>PMID:15958495</ref> <ref>PMID:18614053</ref> <ref>PMID:19907496</ref> | + | [https://www.uniprot.org/uniprot/ESCO1_HUMAN ESCO1_HUMAN] Acetyltransferase required for the establishment of sister chromatid cohesion and couple the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3.<ref>PMID:14576321</ref> <ref>PMID:15958495</ref> <ref>PMID:18614053</ref> <ref>PMID:19907496</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Protein acetylation is a prevalent posttranslational modification that is regulated by diverse acetyltransferase enzymes. While histone acetyltransferases (HATs) have been well characterized both structurally and mechanistically, far less is known about non-histone acetyltransferase enzymes. The human ESCO1 and ESCO2 paralogs acetylate the cohesin complex subunit SMC3 to regulate the separation of sister chromatids during mitosis and meiosis. Missense mutations within the acetyltransferase domain of these proteins correlate with diseases, including endometrial cancers and Roberts Syndrome. Despite their biological importance, the mechanisms underlying acetylation by the ESCO proteins are not understood. Here, we report the X-ray crystal structure of the highly conserved zinc finger-acetyltransferase moiety of ESCO1 with accompanying structure-based mutagenesis and biochemical characterization. We find that the ESCO1acetyltransferase core is structurally homologous to the Gcn5 HAT, but contains unique additional features including a zinc finger and a ~40-residue loop region that appear to play roles in protein stability and SMC3 substrate binding. We identify key residues that play roles in substrate binding and catalysis, and rationalize the functional consequences of disease-associated mutations. Together, these studies reveal the molecular basis for SMC3 acetylation by ESCO1 and have broader implications for understanding the structure/function of non-histone acetyltransferases.
| + | |
| - | | + | |
| - | Molecular Basis for Cohesin Acetylation by Establishment of Sister Chromatid Cohesion N-acetyltransferase ESCO1.,Rivera-Colon Y, Maguire A, Liszczak GP, Olia AS, Marmorstein R J Biol Chem. 2016 Nov 1. pii: jbc.M116.752220. PMID:27803161<ref>PMID:27803161</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5t53" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liszczak, G P]] | + | [[Category: Liszczak GP]] |
| - | [[Category: Maguire, A]] | + | [[Category: Maguire A]] |
| - | [[Category: Marmorstein, R]] | + | [[Category: Marmorstein R]] |
| - | [[Category: Olia, A S]] | + | [[Category: Olia AS]] |
| - | [[Category: Rivera-Colon, Y]] | + | [[Category: Rivera-Colon Y]] |
| - | [[Category: Acetyltransferase]]
| + | |
| - | [[Category: Cohesin]]
| + | |
| - | [[Category: Esco1]]
| + | |
| - | [[Category: Smc3]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ESCO1_HUMAN Acetyltransferase required for the establishment of sister chromatid cohesion and couple the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3.[1] [2] [3] [4]
References
- ↑ Bellows AM, Kenna MA, Cassimeris L, Skibbens RV. Human EFO1p exhibits acetyltransferase activity and is a unique combination of linker histone and Ctf7p/Eco1p chromatid cohesion establishment domains. Nucleic Acids Res. 2003 Nov 1;31(21):6334-43. PMID:14576321
- ↑ Hou F, Zou H. Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesion. Mol Biol Cell. 2005 Aug;16(8):3908-18. Epub 2005 Jun 15. PMID:15958495 doi:http://dx.doi.org/E04-12-1063
- ↑ Zhang J, Shi X, Li Y, Kim BJ, Jia J, Huang Z, Yang T, Fu X, Jung SY, Wang Y, Zhang P, Kim ST, Pan X, Qin J. Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeast. Mol Cell. 2008 Jul 11;31(1):143-51. doi: 10.1016/j.molcel.2008.06.006. PMID:18614053 doi:http://dx.doi.org/10.1016/j.molcel.2008.06.006
- ↑ Terret ME, Sherwood R, Rahman S, Qin J, Jallepalli PV. Cohesin acetylation speeds the replication fork. Nature. 2009 Nov 12;462(7270):231-4. PMID:19907496 doi:nature08550
|
