Structurally conserved alpha-neurotoxin genes encode functionally diverse proteins in the venom of Naja sputatrix.
The structure and organization of the genes encoding the long-chain neurotoxins and four other isoforms of weak neurotoxins in the venom of Naja sputatrix are reported. The genes contained three exons interrupted by two introns, a structure similar to other members of the three-finger toxin family. The proteins encoded by these genes, however, show varied affinity towards nicotinic acetylcholine receptors. Phylogenetic analysis of these genes showed that the weak neurotoxin gene is confined to a distinct group. We also observe that specific mutations of the gene provide the diversity in function in these toxins while maintaining a common structural scaffold. This forms the first report where the molecular basis of evolution of postsynaptic neurotoxins from an ancestral gene can be demonstrated using the same species of snake.
Department of Biochemistry, Faculty of Medicine, National University of Singapore, 8 Medical Drive, 117597 Singapore. bchjeya@nus.edu.sg
Kandiah
K
Jeyaseelan
Siew Lay
SL
Poh
Ramkishen
R
Nair
Arunmozhiarasi
A
Armugam
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016386:Chromosome Walking; D004220:Disulfides / Q000737:chemistry; D004546:Elapid Venoms / Q000378:metabolism*; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005796:Genes / Q000502:physiology*; D007438:Introns / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms; D021122:Protein Subunits; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017385:Sequence Homology; D013379:Substrate Specificity
D004220:Disulfides; D004546:Elapid Venoms; D009498:Neurotoxins; D020033:Protein Isoforms; D021122:Protein Subunits; D011978:Receptors, Nicotinic