8A0W

Crystal structure of the HigA2 antitoxin in complex with operator DNA

8A0W の概要

• エントリーDOI: 10.2210/pdb8a0w/pdb
• 分子名称: Antitoxin HigA-2, DNA (17-MER), PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: antitoxin, higa2, repressor, toxin-antitoxin module, dna binding protein
• 由来する生物種: Vibrio cholerae; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 33674.72

構造登録者

Hadzi, S.,Loris, R. (登録日: 2022-05-30, 公開日: 2023-05-03, 最終更新日: 2024-04-24)

主引用文献

Hadzi, S.,Zivic, Z.,Kovacic, M.,Zavrtanik, U.,Haeserts, S.,Charlier, D.,Plavec, J.,Volkov, A.N.,Lah, J.,Loris, R.
Fuzzy recognition by the prokaryotic transcription factor HigA2 from Vibrio cholerae.
Nat Commun, 15:3105-3105, 2024

PubMed Abstract: Disordered protein sequences can exhibit different binding modes, ranging from well-ordered folding-upon-binding to highly dynamic fuzzy binding. The primary function of the intrinsically disordered region of the antitoxin HigA2 from Vibrio cholerae is to neutralize HigB2 toxin through ultra-high-affinity folding-upon-binding interaction. Here, we show that the same intrinsically disordered region can also mediate fuzzy interactions with its operator DNA and, through interplay with the folded helix-turn-helix domain, regulates transcription from the higBA2 operon. NMR, SAXS, ITC and in vivo experiments converge towards a consistent picture where a specific set of residues in the intrinsically disordered region mediate electrostatic and hydrophobic interactions while "hovering" over the DNA operator. Sensitivity of the intrinsically disordered region to scrambling the sequence, position-specific contacts and absence of redundant, multivalent interactions, point towards a more specific type of fuzzy binding. Our work demonstrates how a bacterial regulator achieves dual functionality by utilizing two distinct interaction modes within the same disordered sequence.

PubMed: 38600130
DOI: 10.1038/s41467-024-47296-3

実験手法

X-RAY DIFFRACTION (2.334 Å)