2ZJB

Crystal structure of the human Dmc1-M200V polymorphic variant

Summary for 2ZJB

• Entry DOI: 10.2210/pdb2zjb/pdb
• Descriptor: Meiotic recombination protein DMC1/LIM15 homolog (1 entity in total)
• Functional Keywords: dna-binding protein, ring protein, octamer, aaa atpase, atp-binding, cell cycle, meiosis, nucleotide-binding, nucleus, polymorphism, recombination
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus (Potential): Q14565
• Total number of polymer chains: 2
• Total formula weight: 75962.48

Authors

Hikiba, J.,Hirota, K.,Kagawa, W.,Ikawa, S.,Kinebuchi, T.,Sakane, I.,Takizawa, Y.,Yokoyama, S.,Mandon-Pepin, B.,Nicolas, A.,Shibata, T.,Ohta, K.,Kurumizaka, H. (deposition date: 2008-03-02, release date: 2008-08-12, Last modification date: 2023-11-01)

Primary citation

Hikiba, J.,Hirota, K.,Kagawa, W.,Ikawa, S.,Kinebuchi, T.,Sakane, I.,Takizawa, Y.,Yokoyama, S.,Mandon-Pepin, B.,Nicolas, A.,Shibata, T.,Ohta, K.,Kurumizaka, H.
Structural and functional analyses of the DMC1-M200V polymorphism found in the human population
Nucleic Acids Res., 36:4181-4190, 2008

PubMed Abstract: The M200V polymorphism of the human DMC1 protein, which is an essential, meiosis-specific DNA recombinase, was found in an infertile patient, raising the question of whether this homozygous human DMC1-M200V polymorphism may cause infertility by affecting the function of the human DMC1 protein. In the present study, we determined the crystal structure of the human DMC1-M200V variant in the octameric-ring form. Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. The corresponding M194V mutation introduced in the Schizosaccharomyces pombe dmc1 gene caused a significant decrease in the meiotic homologous recombination frequency. Together, these structural, biochemical and genetic results provide extensive evidence that the human DMC1-M200V mutation impairs its function, supporting the previous interpretation that this single-nucleotide polymorphism is a source of human infertility.

PubMed: 18566005
DOI: 10.1093/nar/gkn362

Experimental method

X-RAY DIFFRACTION (3.5 Å)