3HH7

Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)

3HH7 の概要

• エントリーDOI: 10.2210/pdb3hh7/pdb
• 分子名称: Muscarinic toxin-like protein 3 homolog (2 entities in total)
• 機能のキーワード: haditoxin, three finger toxin, ophiophagus hannah, snake venom, neurotoxin, nicotinic acetylcholine receptors, acetylcholine receptor inhibitor, disulfide bond, postsynaptic neurotoxin, secreted, toxin
• 由来する生物種: Ophiophagus hannah (King cobra)
• 細胞内の位置: Secreted : A8N286
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15104.88

構造登録者

Roy, A.,Zhou, X.,Chong, M.Z.,D'hoedt, D.,Foo, C.S.,Rajagopalan, N.,Nirthanan, S.,Bertrand, D.,Sivaraman, J.,Kini, R.M. (登録日: 2009-05-15, 公開日: 2010-01-12, 最終更新日: 2024-10-30)

主引用文献

Roy, A.,Zhou, X.,Chong, M.Z.,D'hoedt, D.,Foo, C.S.,Rajagopalan, N.,Nirthanan, S.,Bertrand, D.,Sivaraman, J.,Kini, R.M.
Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)
J.Biol.Chem., 285:8302-8315, 2010

PubMed Abstract: Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of molecular probes and therapeutic agents. Here, we describe the structural and functional characterization of a novel neurotoxin, haditoxin, from the venom of Ophiophagus hannah (King cobra). Haditoxin exhibited novel pharmacology with antagonism toward muscle (alphabetagammadelta) and neuronal (alpha(7), alpha(3)beta(2), and alpha(4)beta(2)) nicotinic acetylcholine receptors (nAChRs) with highest affinity for alpha(7)-nAChRs. The high resolution (1.5 A) crystal structure revealed haditoxin to be a homodimer, like kappa-neurotoxins, which target neuronal alpha(3)beta(2)- and alpha(4)beta(2)-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain alpha-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain alpha-neurotoxins and kappa-neurotoxins notwithstanding, haditoxin exhibited unique blockade of alpha(7)-nAChRs (IC(50) 180 nm), which is recognized by neither short-chain alpha-neurotoxins nor kappa-neurotoxins. This is the first report of a dimeric short-chain alpha-neurotoxin interacting with neuronal alpha(7)-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.

PubMed: 20071329
DOI: 10.1074/jbc.M109.074161

実験手法

X-RAY DIFFRACTION (1.55 Å)