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

File Size Format
63194_1.pdf 2696Kb Adobe PDF View
Title Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra)
Author Roy, Amrita; Zhou, Xingding; Chong, Ming Zhi; D'hoedt, Ddieter; Foo, Chun Shin; Rajagopalan, Nandhaklshore; Nirthanan, S. Niru; Bertrand, Daniel; Sivaraman, J.; Kini, R. Manjunatha
Journal Name Journal of Biological Chemistry
Year Published 2010
Place of publication United States
Publisher American Society for Biochemistry and Molecular Biology
Abstract Snake venoms are a mixture of pharmacologically active proteins and polypeptides that have led to the development of 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 (αβγδ) and neuronal (α7, α3β2, and α4β2) nicotinic acetylcholine receptors (nAChRs) with highest affinity for α7-nAChRs. The high resolution (1.5 Å) crystal structure revealed haditoxin to be a homodimer, like κ-neurotoxins, which target neuronal α3β2- and α4β2-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic short-chain α-neurotoxins. Biochemical studies confirmed that it existed as a non-covalent dimer species in solution. Its structural similarity to short-chain α-neurotoxins and κ-neurotoxins notwithstanding, haditoxin exhibited unique blockade of α7-nAChRs (IC50 180 nm), which is recognized by neither short-chain α-neurotoxins nor κ-neurotoxins. This is the first report of a dimeric short-chain α-neurotoxin interacting with neuronal α7-nAChRs as well as the first homodimeric three-finger toxin to interact with muscle nAChRs.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1074/jbc.M109.074161
Copyright Statement This research was originally published in Journal of Biological Chemistry (JBC). Authors, Structural and Functional Characterization of a Novel Homodimeric Three-finger Neurotoxin from the Venom of Ophiophagus hannah (King Cobra), Journal of Biological Chemistry (JBC) 2010; Vol 285: 8302-8315. Copyright the American Society for Biochemistry and Molecular Biology. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitve version.
Volume 285
Issue Number 11
Page from 8302
Page to 8315
ISSN 0021-9258
Date Accessioned 2010-06-04
Date Available 2010-10-07T04:07:18Z
Language en_AU
Research Centre Griffith Health Institute
Faculty Griffith Health Faculty
Subject Pharmacology and Pharmaceutical Sciences
URI http://hdl.handle.net/10072/34020
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

Show simple item record

Griffith University copyright notice