6HQU

Humanised RadA mutant HumRadA22 in complex with a recombined BRC repeat 8-2

6HQU の概要

• エントリーDOI: 10.2210/pdb6hqu/pdb
• 分子名称: DNA repair and recombination protein RadA, Breast cancer type 2 susceptibility, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: rada, rad51, brc repeat, recombinase, atpase, brca2, oncoprotein
• 由来する生物種: Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1); 詳細
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 235811.60

構造登録者

Pantelejevs, T.,Lindenburg, L.,Hyvonen, M.,Hollfelder, F. (登録日: 2018-09-25, 公開日: 2019-10-09, 最終更新日: 2024-11-06)

主引用文献

Lindenburg, L.H.,Pantelejevs, T.,Gielen, F.,Zuazua-Villar, P.,Butz, M.,Rees, E.,Kaminski, C.F.,Downs, J.A.,Hyvonen, M.,Hollfelder, F.
Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Exchanges of protein sequence modules support leaps in function unavailable through point mutations during evolution. Here we study the role of the two RAD51-interacting modules within the eight binding BRC repeats of BRCA2. We created 64 chimeric repeats by shuffling these modules and measured their binding to RAD51. We found that certain shuffled module combinations were stronger binders than any of the module combinations in the natural repeats. Surprisingly, the contribution from the two modules was poorly correlated with affinities of natural repeats, with a weak BRC8 repeat containing the most effective N-terminal module. The binding of the strongest chimera, BRC8-2, to RAD51 was improved by -2.4 kCal/mol compared to the strongest natural repeat, BRC4. A crystal structure of RAD51:BRC8-2 complex shows an improved interface fit and an extended β-hairpin in this repeat. BRC8-2 was shown to function in human cells, preventing the formation of nuclear RAD51 foci after ionizing radiation.

PubMed: 34772801
DOI: 10.1073/pnas.2017708118

実験手法

X-RAY DIFFRACTION (1.97 Å)