Crystal structure of Hop2–Mnd1 and mechanistic insights into its role in meiotic recombination
Crystal structure of Hop2–Mnd1 and mechanistic insights into its role in meiotic recombination
Abstract In meiotic DNA recombination, the Hop2−Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2−Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra α-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2−Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion.
- Korea Advanced Institute of Science and Technology Korea (Republic of)
- Max Planck Institute of Biochemistry Germany
- Korean Association Of Science and Technology Studies Korea (Republic of)
- Korea Research Institute of Bioscience and Biotechnology Korea (Republic of)
- École Polytechnique Fédérale de Lausanne EPFL Switzerland
Recombination, Genetic, Saccharomyces cerevisiae Proteins, Base Sequence, Sequence Homology, Amino Acid, Chromosomal Proteins, Non-Histone, Protein Conformation, Q, Molecular Sequence Data, Molecular Dynamics Simulation, Crystallography, X-Ray, Meiosis, Structural Biology, Animals, Humans, Amino Acid Sequence, DNA Primers
Recombination, Genetic, Saccharomyces cerevisiae Proteins, Base Sequence, Sequence Homology, Amino Acid, Chromosomal Proteins, Non-Histone, Protein Conformation, Q, Molecular Sequence Data, Molecular Dynamics Simulation, Crystallography, X-Ray, Meiosis, Structural Biology, Animals, Humans, Amino Acid Sequence, DNA Primers
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