Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

Nucleic Acids Res. 2015 Apr 20;43(7):3841-56. doi: 10.1093/nar/gkv172. Epub 2015 Mar 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / physiology
  • Crystallography, X-Ray
  • DNA Primers
  • Humans
  • Meiosis / physiology*
  • Molecular Dynamics Simulation
  • Molecular Sequence Data
  • Protein Conformation
  • Recombination, Genetic*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / physiology
  • Sequence Homology, Amino Acid

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA Primers
  • HOP2 protein, S cerevisiae
  • MND1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins

Associated data

  • OMIM/4Y66