2htf: Difference between revisions
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< | ==The solution structure of the BRCT domain from human polymerase reveals homology with the TdT BRCT domain== | ||
<StructureSection load='2htf' size='340' side='right'caption='[[2htf]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2htf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HTF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HTF FirstGlance]. <br> | |||
</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=2htf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2htf OCA], [https://pdbe.org/2htf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2htf RCSB], [https://www.ebi.ac.uk/pdbsum/2htf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2htf ProSAT]</span></td></tr> | ||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</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/ht/2htf_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=2htf ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The solution structure and dynamics of the BRCT domain from human DNA polymerase mu, implicated in repair of chromosome breaks by nonhomologous end joining (NHEJ), has been determined using NMR methods. BRCT domains are typically involved in protein-protein interactions between factors required for the cellular response to DNA damage. The pol mu BRCT domain is atypical in that, unlike other reported BRCT structures, the pol mu BRCT is neither part of a tandem grouping, nor does it appear to form stable homodimers. Although the sequence of the pol mu BRCT domain has some unique characteristics, particularly the presence of >10% proline residues, it forms the characteristic alphabetaalpha sandwich, in which three alpha helices are arrayed around a central four-stranded beta-sheet. The structure of helix alpha1 is characterized by two solvent-exposed hydrophobic residues, F46 and L50, suggesting that this element may play a role in mediating interactions of pol mu with other proteins. Consistent with this argument, mutation of these residues, as well as the proximal, conserved residue R43, specifically blocked the ability of pol mu to efficiently work together with NHEJ factors Ku and XRCC4-ligase IV to join noncomplementary ends together in vitro. The structural, dynamic, and biochemical evidence reported here identifies a functional surface in the pol mu BRCT domain critical for promoting assembly and activity of the NHEJ machinery. Further, the similarity between the interaction regions of the BRCT domains of pol mu and TdT support the conclusion that they participate in NHEJ as alternate polymerases. | |||
Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining.,DeRose EF, Clarkson MW, Gilmore SA, Galban CJ, Tripathy A, Havener JM, Mueller GA, Ramsden DA, London RE, Lee AL Biochemistry. 2007 Oct 30;46(43):12100-10. Epub 2007 Oct 4. PMID:17915942<ref>PMID:17915942</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2htf" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Clarkson | [[Category: Clarkson MW]] | ||
[[Category: DeRose | [[Category: DeRose EF]] | ||
[[Category: Gilmore | [[Category: Gilmore SA]] | ||
[[Category: Lee | [[Category: Lee AL]] | ||
[[Category: London | [[Category: London RE]] | ||
[[Category: Mueller | [[Category: Mueller GA]] | ||
[[Category: Ramsden | [[Category: Ramsden DA]] | ||
Latest revision as of 22:03, 29 May 2024
The solution structure of the BRCT domain from human polymerase reveals homology with the TdT BRCT domainThe solution structure of the BRCT domain from human polymerase reveals homology with the TdT BRCT domain
Structural highlights
FunctionDPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.[1] [2] [3] [4] 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 PubMedThe solution structure and dynamics of the BRCT domain from human DNA polymerase mu, implicated in repair of chromosome breaks by nonhomologous end joining (NHEJ), has been determined using NMR methods. BRCT domains are typically involved in protein-protein interactions between factors required for the cellular response to DNA damage. The pol mu BRCT domain is atypical in that, unlike other reported BRCT structures, the pol mu BRCT is neither part of a tandem grouping, nor does it appear to form stable homodimers. Although the sequence of the pol mu BRCT domain has some unique characteristics, particularly the presence of >10% proline residues, it forms the characteristic alphabetaalpha sandwich, in which three alpha helices are arrayed around a central four-stranded beta-sheet. The structure of helix alpha1 is characterized by two solvent-exposed hydrophobic residues, F46 and L50, suggesting that this element may play a role in mediating interactions of pol mu with other proteins. Consistent with this argument, mutation of these residues, as well as the proximal, conserved residue R43, specifically blocked the ability of pol mu to efficiently work together with NHEJ factors Ku and XRCC4-ligase IV to join noncomplementary ends together in vitro. The structural, dynamic, and biochemical evidence reported here identifies a functional surface in the pol mu BRCT domain critical for promoting assembly and activity of the NHEJ machinery. Further, the similarity between the interaction regions of the BRCT domains of pol mu and TdT support the conclusion that they participate in NHEJ as alternate polymerases. Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining.,DeRose EF, Clarkson MW, Gilmore SA, Galban CJ, Tripathy A, Havener JM, Mueller GA, Ramsden DA, London RE, Lee AL Biochemistry. 2007 Oct 30;46(43):12100-10. Epub 2007 Oct 4. PMID:17915942[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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