6IMF

Crystal structure of TOXIN/ANTITOXIN complex

6IMF の概要

• エントリーDOI: 10.2210/pdb6imf/pdb
• 分子名称: Cysteine-rich venom protein triflin, Small serum protein 2, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: complex, antitoxin, toxin-antitoxin complex, toxin, toxin/antitoxin
• 由来する生物種: Protobothrops flavoviridis (Habu); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37438.44

構造登録者

Shioi, N.,Tadokoro, T.,Shioi, S.,Hu, Y.,Kurahara, L.H.,Okabe, Y.,Matsubara, H.,Kita, S.,Ose, T.,Kuroki, K.,Maenaka, K.,Terada, S. (登録日: 2018-10-22, 公開日: 2018-12-12, 最終更新日: 2024-10-23)

主引用文献

Shioi, N.,Tadokoro, T.,Shioi, S.,Okabe, Y.,Matsubara, H.,Kita, S.,Ose, T.,Kuroki, K.,Terada, S.,Maenaka, K.
Crystal structure of the complex between venom toxin and serum inhibitor from Viperidae snake.
J. Biol. Chem., 294:1250-1256, 2019

PubMed Abstract: Venomous snakes have endogenous proteins that neutralize the toxicity of their venom components. We previously identified five small serum proteins (SSP-1-SSP-5) from a highly venomous snake belonging to the family Viperidae as inhibitors of various toxins from snake venom. The endogenous inhibitors belong to the prostate secretory protein of 94 amino acids (PSP94) family. SSP-2 interacts with triflin, which is a member of the cysteine-rich secretory protein (CRISP) family that blocks smooth muscle contraction. However, the structural basis for the interaction and the biological roles of these inhibitors are largely unknown. Here, we determined the crystal structure of the SSP-2-triflin complex at 2.3 Å resolution. A concave region centrally located in the N-terminal domain of triflin is fully occupied by the terminal β-strands of SSP-2. SSP-2 does not bind tightly to the C-terminal cysteine-rich domain of triflin; this domain is thought to be responsible for its channel-blocker function. Instead, the cysteine-rich domain is tilted 7.7° upon binding to SSP-2, and the inhibitor appears to sterically hinder triflin binding to calcium channels. These results help explain how an endogenous inhibitor prevents the venomous protein from maintaining homeostasis in the host. Furthermore, this interaction also sheds light on the binding interface between the human homologues PSP94 and CRISP-3, which are up-regulated in prostate and ovarian cancers.

PubMed: 30504218
DOI: 10.1074/jbc.RA118.006840

実験手法

X-RAY DIFFRACTION (2.3 Å)