3al3

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{{STRUCTURE_3al3| PDB=3al3 | SCENE= }}
 
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===Crystal Structure of TopBP1 BRCT7/8-BACH1 peptide complex===
 
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{{ABSTRACT_PUBMED_21127055}}
 
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==Disease==
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==Crystal Structure of TopBP1 BRCT7/8-BACH1 peptide complex==
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[[http://www.uniprot.org/uniprot/FANCJ_HUMAN FANCJ_HUMAN]] Defects in BRIP1 are a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:11301010</ref><ref>PMID:14983014</ref><ref>PMID:16153896</ref><ref>PMID:16116421</ref> Defects in BRIP1 are the cause of Fanconi anemia complementation group J (FANCJ) [MIM:[http://omim.org/entry/609054 609054]]. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.<ref>PMID:16153896</ref><ref>PMID:16116421</ref><ref>PMID:20639400</ref><ref>PMID:16116424</ref><ref>PMID:16116423</ref>
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<StructureSection load='3al3' size='340' side='right'caption='[[3al3]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3al3]] is a 2 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=3AL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AL3 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]] 2.15&#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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=3al3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3al3 OCA], [https://pdbe.org/3al3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3al3 RCSB], [https://www.ebi.ac.uk/pdbsum/3al3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3al3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TOPB1_HUMAN TOPB1_HUMAN] Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR.<ref>PMID:10498869</ref> <ref>PMID:11395493</ref> <ref>PMID:11714696</ref> <ref>PMID:12697828</ref> <ref>PMID:15075294</ref> <ref>PMID:16530042</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The diverse roles of TopBP1 in DNA replication and checkpoint signaling are associated with the scaffolding ability of TopBP1 to initiate various protein-protein interactions. The recognition of the BACH1/FANCJ helicase by TopBP1 is critical for the activation of the DNA replication checkpoint at stalled replication forks and is facilitated by the C-terminal tandem BRCT7/8 domains of TopBP1 and a phosphorylated Thr(1133) binding motif in BACH1. Here we provide the structural basis for this interaction through analysis of the x-ray crystal structures of TopBP1 BRCT7/8 both free and in complex with a BACH1 phospho-peptide. In contrast to canonical BRCT-phospho-peptide recognition, TopBP1 BRCT7/8 undergoes a dramatic conformational change upon BACH1 binding such that the two BRCT repeats pivot about the central BRCT-BRCT interface to provide an extensive and deep peptide-binding cleft. Additionally, we provide the first structural mechanism for Thr(P) recognition among BRCT domains. Together with systematic mutagenesis studies, we highlight the role of key contacts in governing the unique specificity of the TopBP1-BACH1 interaction.
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==Function==
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Molecular basis of BACH1/FANCJ recognition by TopBP1 in DNA replication checkpoint control.,Leung CC, Gong Z, Chen J, Glover JN J Biol Chem. 2011 Feb 11;286(6):4292-301. Epub 2010 Dec 2. PMID:21127055<ref>PMID:21127055</ref>
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[[http://www.uniprot.org/uniprot/TOPB1_HUMAN TOPB1_HUMAN]] Required for DNA replication. Plays a role in the rescue of stalled replication forks and checkpoint control. Binds double-stranded DNA breaks and nicks as well as single-stranded DNA. Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage. Induces a large increase in the kinase activity of ATR.<ref>PMID:10498869</ref><ref>PMID:11395493</ref><ref>PMID:11714696</ref><ref>PMID:12697828</ref><ref>PMID:15075294</ref><ref>PMID:16530042</ref> [[http://www.uniprot.org/uniprot/FANCJ_HUMAN FANCJ_HUMAN]] DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1.<ref>PMID:11301010</ref><ref>PMID:14983014</ref><ref>PMID:16153896</ref><ref>PMID:16116421</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3al3]] is a 2 chain structure with sequence 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=3AL3 OCA].
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</div>
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<div class="pdbe-citations 3al3" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:021127055</ref><references group="xtra"/><references/>
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*[[Topoisomerase binding protein|Topoisomerase binding protein]]
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== References ==
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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: Glover, J N.]]
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[[Category: Large Structures]]
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[[Category: Leung, C C.]]
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[[Category: Glover JN]]
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[[Category: Brct domain-phosphopeptide complex]]
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[[Category: Leung CC]]
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[[Category: Dna binding protein-protein binding complex]]
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Current revision

Crystal Structure of TopBP1 BRCT7/8-BACH1 peptide complex

PDB ID 3al3

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