Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination.
Bottom Line: 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.
Affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.Show MeSH
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Mentions: Of the three heterodimers in the asymmetric unit, the electron densities for the WHD–LZ1 junction as well as the WHDs were visible in Heterodimers I and II. However, the electron densities for the WHD pair in Heterodimer III were not discerned from the noise level. Therefore, the WHD–LZ1 junction is presumed to be conformationally flexible, and the visibility of the WHDs in Heterodimers I and II is ascribed to the crystal packing interactions. Heterodimer II was mostly disordered beyond LZ2, as only a part of LZ3 could be traced (Figure 2A), indicating that the LZ2–LZ3 junction is not rigid. The LZ1–LZ2 junction also appears flexible according to structural superpositions of Heterodimers I and II or Heterodimers I and III, which show that the positions of LZ2 relative to LZ1 are different by about 9° and 5°, respectively (Figure 2B). The WHD–LZ1 junction appears most flexible, because the WHDs in Heterodimer III were indiscernible. The other two junctions may be less flexible, because all three heterodimers retain the curved rod shape (Figure 2A), and because similar molecular envelopes were observed by SAXS analysis of mouse Hop2–Mnd1 in solution (26). Presumably, the overall curved rod-like structure observed in the crystal is likely to be the inherent molecular shape of Hop2–Mnd1 under physiological conditions, while it is conformationally flexible at the three junctions to some degree.
Affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Cancer Metastasis Control Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.