Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination.
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.
Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Hyun-Ah
HA
Kang
Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Ho-Chul
HC
Shin
Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), and Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland.
Alexandra-Styliani
AS
Kalantzi
Chromosome Organization and Dynamics, Max Planck Institute of Biochemistry, Am, Klopferspitz 18, 82152 Martinsried, Germany.
Christopher P
CP
Toseland
Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Hyun-Min
HM
Kim
Chromosome Organization and Dynamics, Max Planck Institute of Biochemistry, Am, Klopferspitz 18, 82152 Martinsried, Germany.
Stephan
S
Gruber
Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), and Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland.
Matteo Dal
MD
Peraro
Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea bhoh@kaist.ac.kr.
Byung-Ha
BH
Oh
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D017931:DNA Primers; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; C113830:HOP2 protein, S cerevisiae; C454441:MND1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins