6FP5

Crystal structure of ZAD-domain of CG2712 protein from D.melanogaster

6FP5 の概要

• エントリーDOI: 10.2210/pdb6fp5/pdb
• 分子名称: CG2712, ZINC ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: architectural protein, insulator, btb-domain, cp190, chromosome, transcription
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23684.55

構造登録者

Boyko, K.M.,Nikolaeva, A.Y.,Bonchuk, A.N.,Kachalova, G.S.,Georgiev, P.G.,Popov, V.O. (登録日: 2018-02-09, 公開日: 2019-08-21, 最終更新日: 2026-02-11)

主引用文献

Bonchuk, A.,Boyko, K.,Fedotova, A.,Nikolaeva, A.,Lushchekina, S.,Khrustaleva, A.,Popov, V.,Georgiev, P.
Structural basis of diversity and homodimerization specificity of zinc-finger-associated domains in Drosophila.
Nucleic Acids Res., 49:2375-2389, 2021

PubMed Abstract: In arthropods, zinc finger-associated domains (ZADs) are found at the N-termini of many DNA-binding proteins with tandem arrays of Cys2-His2 zinc fingers (ZAD-C2H2 proteins). ZAD-C2H2 proteins undergo fast evolutionary lineage-specific expansion and functional diversification. Here, we show that all ZADs from Drosophila melanogaster form homodimers, but only certain ZADs with high homology can also heterodimerize. CG2712, for example, is unable to heterodimerize with its paralog, the previously characterized insulator protein Zw5, with which it shares 46% homology. We obtained a crystal structure of CG2712 protein's ZAD domain that, in spite of a low sequence homology, has similar spatial organization with the only known ZAD structure (from Grauzone protein). Steric clashes prevented the formation of heterodimers between Grauzone and CG2712 ZADs. Using detailed structural analysis, site-directed mutagenesis, and molecular dynamics simulations, we demonstrated that rapid evolutionary acquisition of interaction specificity was mediated by the more energy-favorable formation of homodimers in comparison to heterodimers, and that this specificity was achieved by multiple amino acid substitutions resulting in the formation or breaking of stabilizing interactions. We speculate that specific homodimerization of ZAD-C2H2 proteins is important for their architectural role in genome organization.

PubMed: 33638995
DOI: 10.1093/nar/gkab061

実験手法

X-RAY DIFFRACTION (2 Å)