5LUS

Structures of DHBN domain of Pelecanus crispus BLM helicase

5LUS の概要

• エントリーDOI: 10.2210/pdb5lus/pdb
• 分子名称: BLM helicase (2 entities in total)
• 機能のキーワード: helicase dimerization alpha-helix motif, hydrolase
• 由来する生物種: Pelecanus crispus (Dalmatian pelican)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 76429.34

構造登録者

Shi, J.,Chen, W.-F.,Zhang, B.,Fan, S.-H.,Ai, X.,Liu, N.-N.,Rety, S.,Xi, X.-G. (登録日: 2016-09-09, 公開日: 2017-03-01, 最終更新日: 2024-05-08)

主引用文献

Shi, J.,Chen, W.F.,Zhang, B.,Fan, S.H.,Ai, X.,Liu, N.N.,Rety, S.,Xi, X.G.
A helical bundle in the N-terminal domain of the BLM helicase mediates dimer and potentially hexamer formation.
J. Biol. Chem., 292:5909-5920, 2017

PubMed Abstract: Helicases play a critical role in processes such as replication or recombination by unwinding double-stranded DNA; mutations of these genes can therefore have devastating biological consequences. In humans, mutations in genes of three members of the RecQ family helicases (, , and ) give rise to three strikingly distinctive clinical phenotypes: Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome, respectively. However, the molecular basis for these varying phenotypic outcomes is unclear, in part because a full mechanistic description of helicase activity is lacking. Because the helicase core domains are highly conserved, it has been postulated that functional differences among family members might be explained by significant differences in the N-terminal domains, but these domains are poorly characterized. To help fill this gap, we now describe bioinformatics, biochemical, and structural data for three vertebrate BLM proteins. We pair high resolution crystal structures with SAXS analysis to describe an internal, highly conserved sequence we term the dimerization helical bundle in N-terminal domain (DHBN). We show that, despite the N-terminal domain being loosely structured and potentially lacking a defined three-dimensional structure in general, the DHBN exists as a dimeric structure required for higher order oligomer assembly. Interestingly, the unwinding amplitude and rate decrease as BLM is assembled from dimer into hexamer, and also, the stable DHBN dimer can be dissociated upon ATP hydrolysis. Thus, the structural and biochemical characterizations of N-terminal domains will provide new insights into how the N-terminal domain affects the structural and functional organization of the full BLM molecule.

PubMed: 28228481
DOI: 10.1074/jbc.M116.761510

実験手法

X-RAY DIFFRACTION (1.433 Å)