2LE8

The protein complex for DNA replication

2LE8 の概要

• エントリーDOI: 10.2210/pdb2le8/pdb
• NMR情報: BMRB: 17702
• 分子名称: DNA replication licensing factor MCM6, DNA replication factor Cdt1 (2 entities in total)
• 機能のキーワード: dna replication, replication
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: Q14566 Q9H211
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16665.79

構造登録者

Liu, C.,Wei, Z.,Zhu, G. (登録日: 2011-06-14, 公開日: 2012-12-19, 最終更新日: 2024-05-15)

主引用文献

Liu, C.,Wu, R.,Zhou, B.,Wang, J.,Wei, Z.,Tye, B.K.,Liang, C.,Zhu, G.
Structural insights into the Cdt1-mediated MCM2-7 chromatin loading
Nucleic Acids Res., 40:3208-3217, 2012

PubMed Abstract: Initiation of DNA replication in eukaryotes is exquisitely regulated to ensure that DNA replication occurs exactly once in each cell division. A conserved and essential step for the initiation of eukaryotic DNA replication is the loading of the mini-chromosome maintenance 2-7 (MCM2-7) helicase onto chromatin at replication origins by Cdt1. To elucidate the molecular mechanism of this event, we determined the structure of the human Cdt1-Mcm6 binding domains, the Cdt1(410-440)/MCM6(708-821) complex by NMR. Our structural and site-directed mutagenesis studies showed that charge complementarity is a key determinant for the specific interaction between Cdt1 and Mcm2-7. When this interaction was interrupted by alanine substitutions of the conserved interacting residues, the corresponding yeast Cdt1 and Mcm6 mutants were defective in DNA replication and the chromatin loading of Mcm2, resulting in cell death. Having shown that Cdt1 and Mcm6 interact through their C-termini, and knowing that Cdt1 is tethered to Orc6 during the loading of MCM2-7, our results suggest that the MCM2-7 hexamer is loaded with its C terminal end facing the ORC complex. These results provide a structural basis for the Cdt1-mediated MCM2-7 chromatin loading.

PubMed: 22140117
DOI: 10.1093/nar/gkr1118

実験手法

SOLUTION NMR