6JTZ

Crystal Structure of hRecQ1_D2-Zn-WH containing mutation on beta-hairpin

6JTZ の概要

• エントリーDOI: 10.2210/pdb6jtz/pdb
• 分子名称: ATP-dependent DNA helicase Q1, ZINC ION (3 entities in total)
• 機能のキーワード: recq1, helicase, dna-binding protein, zn-binding domain, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80382.11

構造登録者

Das, T.,Mukhopadhyay, S.,Bose, M.,Das, A.K.,Ganguly, A. (登録日: 2019-04-12, 公開日: 2020-04-15, 最終更新日: 2023-11-22)

主引用文献

Mukhopadhyay, S.,Das, T.,Bose, M.,Jain, C.K.,Chakraborty, M.,Mukherjee, S.,Shikha, K.,Das, A.K.,Ganguly, A.
Residues at the interface between zinc binding and winged helix domains of human RECQ1 play a significant role in DNA strand annealing activity.
Nucleic Acids Res., 2021

PubMed Abstract: RECQ1 is the shortest among the five human RecQ helicases comprising of two RecA like domains, a zinc-binding domain and a RecQ C-terminal domain containing the winged-helix (WH). Mutations or deletions on the tip of a β-hairpin located in the WH domain are known to abolish the unwinding activity. Interestingly, the same mutations on the β-hairpin of annealing incompetent RECQ1 mutant (RECQ1T1) have been reported to restore its annealing activity. In an attempt to unravel the strand annealing mechanism, we have crystallized a fragment of RECQ1 encompassing D2-Zn-WH domains harbouring mutations on the β-hairpin. From our crystal structure data and interface analysis, we have demonstrated that an α-helix located in zinc-binding domain potentially interacts with residues of WH domain, which plays a significant role in strand annealing activity. We have shown that deletion of the α-helix or mutation of specific residues on it restores strand annealing activity of annealing deficient constructs of RECQ1. Our results also demonstrate that mutations on the α-helix induce conformational changes and affects DNA stimulated ATP hydrolysis and unwinding activity of RECQ1. Our study, for the first time, provides insight into the conformational requirements of the WH domain for efficient strand annealing by human RECQ1.

PubMed: 34751402
DOI: 10.1093/nar/gkab968

実験手法

X-RAY DIFFRACTION (2.797 Å)