7C9C

Human DMC1 pre-synaptic complexes

7C9C の概要

• エントリーDOI: 10.2210/pdb7c9c/pdb
• EMDBエントリー: 30311
• 分子名称: DNA (5'-D(P*TP*TP*TP*TP*TP*TP*TP*TP*T)-3'), Meiotic recombination protein DMC1/LIM15 homolog, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: meiotic homologous recombination, dna repair, atpase, recombination, recombination-dna complex, recombination/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117524.69

構造登録者

Luo, S.C.,Yeh, H.Y.,Chi, P.,Ho, M.C.,Tsai, M.D. (登録日: 2020-06-05, 公開日: 2020-11-25, 最終更新日: 2025-04-09)

主引用文献

Luo, S.C.,Yeh, H.Y.,Lan, W.H.,Wu, Y.M.,Yang, C.H.,Chang, H.Y.,Su, G.C.,Lee, C.Y.,Wu, W.J.,Li, H.W.,Ho, M.C.,Chi, P.,Tsai, M.D.
Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures.
Nat Commun, 12:115-115, 2021

PubMed Abstract: Both high-fidelity and mismatch-tolerant recombination, catalyzed by RAD51 and DMC1 recombinases, respectively, are indispensable for genomic integrity. Here, we use cryo-EM, MD simulation and functional analysis to elucidate the structural basis for the mismatch tolerance of DMC1. Structural analysis of DMC1 presynaptic and postsynaptic complexes suggested that the lineage-specific Loop 1 Gln244 (Met243 in RAD51) may help stabilize DNA backbone, whereas Loop 2 Pro274 and Gly275 (Val273/Asp274 in RAD51) may provide an open "triplet gate" for mismatch tolerance. In support, DMC1-Q244M displayed marked increase in DNA dynamics, leading to unobservable DNA map. MD simulation showed highly dispersive mismatched DNA ensemble in RAD51 but well-converged DNA in DMC1 and RAD51-V273P/D274G. Replacing Loop 1 or Loop 2 residues in DMC1 with RAD51 counterparts enhanced DMC1 fidelity, while reciprocal mutations in RAD51 attenuated its fidelity. Our results show that three Loop 1/Loop 2 residues jointly enact contrasting fidelities of DNA recombinases.

PubMed: 33446654
DOI: 10.1038/s41467-020-20258-1

実験手法

ELECTRON MICROSCOPY (3.33 Å)