|
|
(8 intermediate revisions not shown.) |
Line 1: |
Line 1: |
- | {{Seed}} | |
- | [[Image:2khu.png|left|200px]] | |
| | | |
- | <!-- | + | ==Solution Structure of the Ubiquitin-Binding Motif of Human Polymerase Iota== |
- | The line below this paragraph, containing "STRUCTURE_2khu", creates the "Structure Box" on the page.
| + | <StructureSection load='2khu' size='340' side='right'caption='[[2khu]]' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2khu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_sp._'group_G' Streptococcus sp. 'group G']. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KHU FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2khu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2khu OCA], [https://pdbe.org/2khu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2khu RCSB], [https://www.ebi.ac.uk/pdbsum/2khu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2khu ProSAT]</span></td></tr> |
- | {{STRUCTURE_2khu| PDB=2khu | SCENE= }}
| + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/SPG2_STRSG SPG2_STRSG] [https://www.uniprot.org/uniprot/POLI_HUMAN POLI_HUMAN] Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.<ref>PMID:11013228</ref> <ref>PMID:11251121</ref> <ref>PMID:11387224</ref> <ref>PMID:12410315</ref> <ref>PMID:14630940</ref> <ref>PMID:15199127</ref> <ref>PMID:15254543</ref> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/2khu_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </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=2khu ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Translesion synthesis is an essential cell survival strategy to promote replication after DNA damage. The accumulation of Y family polymerases (pol) iota and Rev1 at the stalled replication machinery is mediated by the ubiquitin-binding motifs (UBMs) of the polymerases and enhanced by PCNA monoubiquitination. We report the solution structures of the C-terminal UBM of human pol iota and its complex with ubiquitin. Distinct from other ubiquitin-binding domains, the UBM binds to the hydrophobic surface of ubiquitin centered at L8. Accordingly, mutation of L8A, but not I44A, of ubiquitin abolishes UBM binding. Human pol iota contains two functional UBMs, both contributing to replication foci formation. In contrast, only the second UBM of Saccharomyces cerevisiae Rev1 binds to ubiquitin and is essential for Rev1-dependent cell survival and mutagenesis. Point mutations disrupting the UBM-ubiquitin interaction also impair the accumulation of pol iota in replication foci and Rev1-mediated DNA damage tolerance in vivo. |
| | | |
- | ===Solution Structure of the Ubiquitin-Binding Motif of Human Polymerase Iota===
| + | Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.,Bomar MG, D'Souza S, Bienko M, Dikic I, Walker GC, Zhou P Mol Cell. 2010 Feb 12;37(3):408-17. PMID:20159559<ref>PMID:20159559</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 2khu" style="background-color:#fffaf0;"></div> |
| | | |
- | <!--
| + | ==See Also== |
- | The line below this paragraph, {{ABSTRACT_PUBMED_20159559}}, adds the Publication Abstract to the page
| + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
- | (as it appears on PubMed at http://www.pubmed.gov), where 20159559 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_20159559}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | [[Category: Homo sapiens]] |
- | 2KHU is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptococcus_sp.,_homo_sapiens Streptococcus sp., homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KHU OCA].
| + | [[Category: Large Structures]] |
- | | + | [[Category: Streptococcus sp. 'group G']] |
- | ==Reference== | + | [[Category: Bienko M]] |
- | <ref group="xtra">PMID:20159559</ref><references group="xtra"/> | + | [[Category: Bomar MG]] |
- | [[Category: DNA-directed DNA polymerase]] | + | [[Category: D'Souza S]] |
- | [[Category: Streptococcus sp., homo sapiens]] | + | [[Category: Dikic I]] |
- | [[Category: Bienko, M.]] | + | [[Category: Walker G]] |
- | [[Category: Bomar, M G.]] | + | |
- | [[Category: Dikic, I.]] | + | |
- | [[Category: Souza, S D.]] | + | |
- | [[Category: Walker, G.]] | + | |
- | [[Category: Immunoglobulin g-binding protein]] | + | |
- | [[Category: Polymerase iota]]
| + | |
- | [[Category: Tl]]
| + | |
- | [[Category: Transferase-protein binding complex]]
| + | |
- | [[Category: Translesion synthesis]]
| + | |
- | [[Category: Ubiquitin-binding domain]]
| + | |
- | [[Category: Ubiquitin-binding protein]]
| + | |
- | [[Category: Ubm]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 3 14:24:46 2010''
| + | |
| Structural highlights
Function
SPG2_STRSG POLI_HUMAN Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunogobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity.[1] [2] [3] [4] [5] [6] [7]
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
Translesion synthesis is an essential cell survival strategy to promote replication after DNA damage. The accumulation of Y family polymerases (pol) iota and Rev1 at the stalled replication machinery is mediated by the ubiquitin-binding motifs (UBMs) of the polymerases and enhanced by PCNA monoubiquitination. We report the solution structures of the C-terminal UBM of human pol iota and its complex with ubiquitin. Distinct from other ubiquitin-binding domains, the UBM binds to the hydrophobic surface of ubiquitin centered at L8. Accordingly, mutation of L8A, but not I44A, of ubiquitin abolishes UBM binding. Human pol iota contains two functional UBMs, both contributing to replication foci formation. In contrast, only the second UBM of Saccharomyces cerevisiae Rev1 binds to ubiquitin and is essential for Rev1-dependent cell survival and mutagenesis. Point mutations disrupting the UBM-ubiquitin interaction also impair the accumulation of pol iota in replication foci and Rev1-mediated DNA damage tolerance in vivo.
Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1.,Bomar MG, D'Souza S, Bienko M, Dikic I, Walker GC, Zhou P Mol Cell. 2010 Feb 12;37(3):408-17. PMID:20159559[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tissier A, Frank EG, McDonald JP, Iwai S, Hanaoka F, Woodgate R. Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota. EMBO J. 2000 Oct 2;19(19):5259-66. PMID:11013228 doi:http://dx.doi.org/10.1093/emboj/19.19.5259
- ↑ Bebenek K, Tissier A, Frank EG, McDonald JP, Prasad R, Wilson SH, Woodgate R, Kunkel TA. 5'-Deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro. Science. 2001 Mar 16;291(5511):2156-9. PMID:11251121 doi:http://dx.doi.org/10.1126/science.1058386
- ↑ Frank EG, Tissier A, McDonald JP, Rapic-Otrin V, Zeng X, Gearhart PJ, Woodgate R. Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template. EMBO J. 2001 Jun 1;20(11):2914-22. PMID:11387224 doi:http://dx.doi.org/10.1093/emboj/20.11.2914
- ↑ Faili A, Aoufouchi S, Flatter E, Gueranger Q, Reynaud CA, Weill JC. Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota. Nature. 2002 Oct 31;419(6910):944-7. PMID:12410315 doi:http://dx.doi.org/10.1038/nature01117
- ↑ Haracska L, Prakash L, Prakash S. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. PMID:14630940 doi:10.1101/gad.1146103
- ↑ Washington MT, Minko IG, Johnson RE, Wolfle WT, Harris TM, Lloyd RS, Prakash S, Prakash L. Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa. Mol Cell Biol. 2004 Jul;24(13):5687-93. PMID:15199127 doi:http://dx.doi.org/10.1128/MCB.24.13.5687-5693.2004
- ↑ Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing. Nature. 2004 Jul 15;430(6997):377-80. PMID:15254543 doi:10.1038/nature02692
- ↑ Bomar MG, D'Souza S, Bienko M, Dikic I, Walker GC, Zhou P. Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1. Mol Cell. 2010 Feb 12;37(3):408-17. PMID:20159559 doi:10.1016/j.molcel.2009.12.038
|