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- | {{Seed}} | |
- | [[Image:3gv5.png|left|200px]] | |
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- | <!-- | + | ==Human DNA polymerase iota in complex with T template DNA and incoming ddADP== |
- | The line below this paragraph, containing "STRUCTURE_3gv5", creates the "Structure Box" on the page.
| + | <StructureSection load='3gv5' size='340' side='right'caption='[[3gv5]], [[Resolution|resolution]] 2.00Å' 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'>[[3gv5]] 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=3GV5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GV5 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">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADI:2,3-DIDEOXYADENOSINE-5-DIPHOSPHATE'>ADI</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
- | {{STRUCTURE_3gv5| PDB=3gv5 | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gv5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gv5 OCA], [https://pdbe.org/3gv5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gv5 RCSB], [https://www.ebi.ac.uk/pdbsum/3gv5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gv5 ProSAT]</span></td></tr> |
| + | </table> |
| + | == Function == |
| + | [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/gv/3gv5_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3gv5 ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity. |
| | | |
- | ===Human DNA polymerase iota in complex with T template DNA and incoming ddADP===
| + | Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota.,Kirouac KN, Ling H EMBO J. 2009 Jun 3;28(11):1644-54. PMID:19440206<ref>PMID:19440206</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 3gv5" style="background-color:#fffaf0;"></div> |
| | | |
- | <!--
| + | ==See Also== |
- | The line below this paragraph, {{ABSTRACT_PUBMED_19440206}}, 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 19440206 is the PubMed ID number.
| + | == References == |
- | -->
| + | <references/> |
- | {{ABSTRACT_PUBMED_19440206}}
| + | __TOC__ |
- | | + | </StructureSection> |
- | ==About this Structure== | + | |
- | 3GV5 is a 6 chains structure of sequences 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=3GV5 OCA].
| + | |
- | | + | |
- | ==Reference== | + | |
- | <ref group="xtra">PMID:19440206</ref><references group="xtra"/> | + | |
- | [[Category: DNA-directed DNA polymerase]]
| + | |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Kirouac, K N.]] | + | [[Category: Large Structures]] |
- | [[Category: Ling, H.]] | + | [[Category: Kirouac KN]] |
- | [[Category: Dna damage]] | + | [[Category: Ling H]] |
- | [[Category: Dna repair]]
| + | |
- | [[Category: Dna replication]]
| + | |
- | [[Category: Dna synthesis]]
| + | |
- | [[Category: Dna-binding]]
| + | |
- | [[Category: Dna-directed dna polymerase]]
| + | |
- | [[Category: Error prone replication]]
| + | |
- | [[Category: Magnesium]]
| + | |
- | [[Category: Metal-binding]]
| + | |
- | [[Category: Mutator protein]]
| + | |
- | [[Category: Nucleotidyltransferase]]
| + | |
- | [[Category: Nucleus]]
| + | |
- | [[Category: Polymerase iota]]
| + | |
- | [[Category: Polymorphism]]
| + | |
- | [[Category: Schiff base]]
| + | |
- | [[Category: Transferase]]
| + | |
- | [[Category: Transferase/dna complex]]
| + | |
- | [[Category: Y-family polymerase]]
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- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 1 09:54:47 2009''
| + | |
| Structural highlights
Function
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
Human DNA polymerase iota (pol iota) is a unique member of Y-family polymerases, which preferentially misincorporates nucleotides opposite thymines (T) and halts replication at T bases. The structural basis of the high error rates remains elusive. We present three crystal structures of pol complexed with DNA containing a thymine base, paired with correct or incorrect incoming nucleotides. A narrowed active site supports a pyrimidine to pyrimidine mismatch and excludes Watson-Crick base pairing by pol. The template thymine remains in an anti conformation irrespective of incoming nucleotides. Incoming ddATP adopts a syn conformation with reduced base stacking, whereas incorrect dGTP and dTTP maintain anti conformations with normal base stacking. Further stabilization of dGTP by H-bonding with Gln59 of the finger domain explains the preferential T to G mismatch. A template 'U-turn' is stabilized by pol and the methyl group of the thymine template, revealing the structural basis of T stalling. Our structural and domain-swapping experiments indicate that the finger domain is responsible for pol's high error rates on pyrimidines and determines the incorporation specificity.
Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota.,Kirouac KN, Ling H EMBO J. 2009 Jun 3;28(11):1644-54. PMID:19440206[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
- ↑ Kirouac KN, Ling H. Structural basis of error-prone replication and stalling at a thymine base by human DNA polymerase iota. EMBO J. 2009 Jun 3;28(11):1644-54. PMID:19440206 doi:10.1038/emboj.2009.122
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