View source for 5t2f


==Structure of the FHA1 domain of Rad53 bound to the BRCT domain of Dbf4==
<StructureSection load='5t2f' size='340' side='right' caption='[[5t2f]], [[Resolution|resolution]] 2.66&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5t2f]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T2F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5t2s|5t2s]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></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=5t2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t2f OCA], [http://pdbe.org/5t2f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t2f RCSB], [http://www.ebi.ac.uk/pdbsum/5t2f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t2f ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/DBF4_YEAST DBF4_YEAST]] Regulatory subunit of the CDC7-DBF4 kinase, also called DBF4-dependent kinase (DDK), which is involved in cell cycle regulation of premitotic and premeiotic chromosome replication and in chromosome segregation. DDK plays an essential role in initiating DNA replication at replication origins by phosphorylating the MCM2 and MCM4 subunits of the MCM2-7 helicase complex. DBF4 recruits the catalytic subunit CDC7 to MCM2 and to origins of replication. DDK has also postreplicative functions in meiosis. DDK phosphorylates the meiosis-specific double-strand break protein MER2 for initiation of meiotic recombination. Interacts with CDC5 during meiosis to promote double-strand breaks and monopolar spindle orientation. Inhibits CDC5 activity during mitosis through direct binding to its PBD.<ref>PMID:8066465</ref> <ref>PMID:12441400</ref> <ref>PMID:16319063</ref> <ref>PMID:17018296</ref> <ref>PMID:19013276</ref> <ref>PMID:18245450</ref> <ref>PMID:19692334</ref> <ref>PMID:19478884</ref> <ref>PMID:20436286</ref> <ref>PMID:21036905</ref> <ref>PMID:20170732</ref> <ref>PMID:20054399</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Forkhead-associated (FHA) domains are phosphopeptide recognition modules found in many signaling proteins. The Saccharomyces cerevisiae protein kinase Rad53 is a key regulator of the DNA damage checkpoint and uses its two FHA domains to interact with multiple binding partners during the checkpoint response. One of these binding partners is the Dbf4-dependent kinase (DDK), a heterodimer composed of the Cdc7 kinase and its regulatory subunit Dbf4. Binding of Rad53 to DDK, through its N-terminal FHA (FHA1) domain, ultimately inhibits DDK kinase activity, thereby preventing firing of late origins. We have previously found that the FHA1 domain of Rad53 binds simultaneously to Dbf4 and a phosphoepitope, suggesting that this domain functions as an 'AND' logic gate. Here, we present the crystal structures of the FHA1 domain of Rad53 bound to Dbf4, in the presence and absence of a Cdc7 phosphorylated peptide. Our results reveal how the FHA1 uses a canonical binding interface to recognize the Cdc7 phosphopeptide and a non-canonical interface to bind Dbf4. Based on these data we propose a mechanism to explain how Rad53 enhances the specificity of FHA1-mediated transient interactions.

'AND' logic gates at work: Crystal structure of Rad53 bound to Dbf4 and Cdc7.,Almawi AW, Matthews LA, Larasati, Myrox P, Boulton S, Lai C, Moraes T, Melacini G, Ghirlando R, Duncker BP, Guarne A Sci Rep. 2016 Sep 29;6:34237. doi: 10.1038/srep34237. PMID:27681475<ref>PMID:27681475</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5t2f" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dual-specificity kinase]]
[[Category: Almawi, A W]]
[[Category: Guarne, A]]
[[Category: Matthews, L A]]
[[Category: Brct]]
[[Category: Cell cycle]]
[[Category: Fha]]
[[Category: Protein chimera]]