Crystal structure of the coiled-coil dimerization motif of geminin: structural and functional insights on DNA replication regulation

J Mol Biol. 2004 Sep 3;342(1):275-87. doi: 10.1016/j.jmb.2004.06.065.


We have determined the crystal structure of the coiled-coil domain of human geminin, a DNA synthesis inhibitor in higher eukaryotes. We show that a peptide encompassing the five heptad repeats of the geminin leucine zipper (LZ) domain is a dimeric parallel coiled coil characterized by a unique pattern of internal polar residues and a negatively charged surface that may target the basic domain of interacting partners. We show that the LZ domain itself is not sufficient to inhibit DNA synthesis but upstream and downstream residues are required. Analysis of a functional form of geminin by density sedimentation indicates an oligomeric structure. X-ray solution scattering experiments performed on a non-functional form of geminin having upstream basic residues and the LZ domain show a tetramer structure. Altogether, these results give a consistent identification and mapping of geminin interacting regions onto structurally important domains. They also suggest that oligomerization properties of geminin may be implicated in its inhibitory activity of DNA synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / genetics
  • Circular Dichroism
  • Crystallography, X-Ray
  • DNA Replication*
  • Dimerization
  • Geminin
  • Humans
  • Leucine Zippers
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Thermodynamics


  • Cell Cycle Proteins
  • GMNN protein, human
  • Geminin

Associated data

  • PDB/1T6F