7BDX

Armadillo domain of HSF2BP in complex with BRCA2 peptide

7BDX の概要

• エントリーDOI: 10.2210/pdb7bdx/pdb
• 分子名称: Heat shock factor 2-binding protein, Breast cancer type 2 susceptibility protein, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: hsf2bp, brca2, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 108922.85

構造登録者

Le Du, M.H.,Zinn-Justin, S.,Ghouil, R.,Miron, S.,Legrand, P. (登録日: 2020-12-22, 公開日: 2021-07-07, 最終更新日: 2024-11-13)

主引用文献

Ghouil, R.,Miron, S.,Koornneef, L.,Veerman, J.,Paul, M.W.,Le Du, M.H.,Sleddens-Linkels, E.,van Rossum-Fikkert, S.E.,van Loon, Y.,Felipe-Medina, N.,Pendas, A.M.,Maas, A.,Essers, J.,Legrand, P.,Baarends, W.M.,Kanaar, R.,Zinn-Justin, S.,Zelensky, A.N.
BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination.
Nat Commun, 12:4605-4605, 2021

PubMed Abstract: BRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity - the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, from mBrca2 disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.

PubMed: 34326328
DOI: 10.1038/s41467-021-24871-6

実験手法

X-RAY DIFFRACTION (2.6 Å)