Please use this identifier to cite or link to this item:
Title: Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (King cobra)
Authors: Roy, A.
Zhou, X. 
Chong, M.Z.
D'Hoedt, D.
Foo, C.S.
Rajagopalan, N.
Nirthanan, S.
Bertrand, D.
Sivaraman, J. 
Manjunatha Kini, R. 
Issue Date: 12-Mar-2010
Citation: Roy, A., Zhou, X., Chong, M.Z., D'Hoedt, D., Foo, C.S., Rajagopalan, N., Nirthanan, S., Bertrand, D., Sivaraman, J., Manjunatha Kini, R. (2010-03-12). Structural and functional characterization of a novel homodimeric three-finger neurotoxin from the venom of Ophiophagus hannah (King cobra). Journal of Biological Chemistry 285 (11) : 8302-8315. ScholarBank@NUS Repository.
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 (αβγδ) and neuronal (α7, α3β2, and α4β 2) 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 α 4β2-nAChRs. Interestingly however, the monomeric subunits of haditoxin were composed of a three-finger protein fold typical of curaremimetic shortchain 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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M109.074161
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Oct 21, 2021


checked on Oct 21, 2021

Page view(s)

checked on Oct 14, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.