5t2f | pdb_00005t2f

Structure of the FHA1 domain of Rad53 bound to the BRCT domain of Dbf4

spinqualitylabelsall models 5t2f, resolution 2.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5t2f is a 4 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.66Å Ligands: EDO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RAD53_YEAST Controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints. Phosphorylates proteins on serine, threonine, and tyrosine. Prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. Seems to be involved in the phosphorylation of RPH1. 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Protein kinase Spk1

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