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: The two WHDs are closely juxtaposed and interact with each other (Figure 5A). The WHD–WHD interface, burying a surface area of 250.6 Å2, comprises of many hydrophobic residues (Pro22, Ile55, Leu65, Leu67 of Hop2; Ile25, Ile63, Tyr68, Trp70, Phe72 of Mnd1) and two charged residues (Lys21 of Hop2; Asp61 of Mnd1) forming a salt bridge (Figure 5A). These observations indicate that the WHDs adopt a fixed, rather than random, relative orientation. Consistent with this notion, the WHDs in Heterodimers I and II exhibit virtually the same orientations (Figure 5B). Remarkably, all of the interface lining residues are highly conserved except Ile55 of Hop2 (Figure 3A and B; orange boxes), indicating that the juxtaposition of the WHDs in the observed orientations is likely to be an evolutionary conserved feature important for the molecular function of Hop2–Mnd1. A further confirmation of the stability of the WHD–WHD interface comes from molecular dynamics (MD) simulations, as described in the next section.
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.