2od8
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Structure of a peptide derived from Cdc9 bound to PCNA
OverviewOverview
There is compelling evidence that proliferating cell nuclear antigen, (PCNA), a DNA sliding clamp, co-ordinates the processing and joining of, Okazaki fragments during eukaryotic DNA replication. However, a detailed, mechanistic understanding of functional PCNA:ligase I interactions has, been incomplete. Here we present the co-crystal structure of yeast PCNA, with a peptide encompassing the conserved PCNA interaction motif of Cdc9, yeast DNA ligase I. The Cdc9 peptide contacts both the inter-domain, connector loop (IDCL) and residues near the C-terminus of PCNA., Complementary mutational and biochemical results demonstrate that these, two interaction interfaces are required for complex formation both in the, absence of DNA and when PCNA is topologically linked to DNA. Similar to, the functionally homologous human proteins, yeast RFC interacts with and, inhibits Cdc9 DNA ligase whereas the addition of PCNA alleviates, inhibition by RFC. Here we show that the ability of PCNA to overcome, RFC-mediated inhibition of Cdc9 is dependent upon both the IDCL and the, C-terminal interaction interfaces of PCNA. Together these results, demonstrate the functional significance of the beta-zipper structure, formed between the C-terminal domain of PCNA and Cdc9 and reveal, differences in the interactions of FEN-1 and Cdc9 with the two PCNA, interfaces that may contribute to the co-ordinated, sequential action of, these enzymes.
About this StructureAbout this Structure
2OD8 is a Protein complex structure of sequences from Saccharomyces cerevisiae. Active as DNA ligase (ATP), with EC number 6.5.1.1 Full crystallographic information is available from OCA.
ReferenceReference
The C-terminal domain of yeast PCNA is required for physical and functional interactions with Cdc9 DNA ligase., Vijayakumar S, Chapados BR, Schmidt KH, Kolodner RD, Tainer JA, Tomkinson AE, Nucleic Acids Res. 2007;35(5):1624-37. Epub 2007 Feb 18. PMID:17308348
Page seeded by OCA on Wed Nov 21 13:08:08 2007