Structure, function and evolution of three-finger toxins: Mini proteins with multiple targets

• Published in: Toxicon (Oxford) Vol. 56; no. 6; pp. 855 - 867
• Main Authors: Kini, R. Manjunatha, Doley, Robin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-11-2010; Elsevier
• Subjects: Amino Acid Sequence; Animal poisons toxicology. Antivenoms; Animals; Biological and medical sciences; Calciseptine; Cardiotoxin; Cytotoxin; Dimeric three finger toxin; Disulfides - chemistry; Evolution; Evolution, Molecular; Fasciculin; Functional site; Ion channels; Medical sciences; Mini; Models, Molecular; Molecular Sequence Data; Muscarinic toxin; Mutations; Neurotoxins - chemistry; Neurotoxins - metabolism; Neurotoxins - pharmacology; Post-synaptic neurotoxin; Protein Structure, Tertiary; Proteins; protein–protein interaction; Receptors; Segments; Snake venom; Snake Venoms - chemistry; Snakes; Structure-Activity Relationship; Substrate Specificity; Toxicology; Toxin evolution; Toxins; Cardiotoxin; Snake venom; Muscarinic toxin; Post-synaptic neurotoxin; Fasciculin; protein–protein interaction; Toxin evolution; Cytotoxin; Calciseptine; Functional site; Dimeric three finger toxin; Interaction; Animal origin; Protein; Ophidia; Toxin; Vertebrata; Target; Venom; Neurotoxin; Evolution; Reptilia; protein-protein interaction
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2010.07.010

Snake venoms are complex mixtures of pharmacologically active peptides and proteins. These protein toxins belong to a small number of superfamilies of proteins. Three-finger toxins belong to a superfamily of non-enzymatic proteins found in all families of snakes. They have a common structure of three β-stranded loops extending from a central core containing all four conserved disulphide bonds. Despite the common scaffold, they bind to different receptors/acceptors and exhibit a wide variety of biological effects. Thus, the structure–function relationships of this group of toxins are complicated and challenging. Studies have shown that the functional sites in these ‘sibling’ toxins are located on various segments of the molecular surface. Targeting to a wide variety of receptors and ion channels and hence distinct functions in this group of mini proteins is achieved through a combination of accelerated rate of exchange of segments as well as point mutations in exons. In this review, we describe the structural and functional diversity, structure–function relationships and evolution of this group of snake venom toxins.