Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6

J Biol Chem. 2010 Apr 23;285(17):12469-73. doi: 10.1074/jbc.C109.094599. Epub 2010 Mar 4.

Abstract

The minichromosome maintenance (Mcm) 2-7 complex is the replicative helicase in eukaryotic species, and it plays essential roles in the initiation and elongation phases of DNA replication. During late M and early G(1), the Mcm2-7 complex is loaded onto chromatin to form prereplicative complex in a Cdt1-dependent manner. However, the detailed molecular mechanism of this loading process is still elusive. In this study, we demonstrate that the previously uncharacterized C-terminal domain of human Mcm6 is the Cdt1 binding domain (CBD) and present its high resolution NMR structure. The structure of CBD exhibits a typical "winged helix" fold that is generally involved in protein-nucleic acid interaction. Nevertheless, the CBD failed to interact with DNA in our studies, indicating that it is specific for protein-protein interaction. The CBD-Cdt1 interaction involves the helix-turn-helix motif of CBD. The results reported here provide insight into the molecular mechanism of Mcm2-7 chromatin loading and prereplicative complex assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Chromatin / chemistry
  • Chromatin / metabolism
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • G1 Phase / physiology
  • Helix-Turn-Helix Motifs
  • Humans
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Protein Binding / physiology
  • Protein Structure, Tertiary

Substances

  • CDT1 protein, human
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • DNA Helicases
  • MCM6 protein, human
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 6
  • Minichromosome Maintenance Complex Component 7

Associated data

  • PDB/2KLQ