Chemistry:Irditoxin
Irditoxin subunit A | |||||||
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Identifiers | |||||||
Organism | |||||||
Symbol | 3NBA | ||||||
PDB | 2H7Z (ECOD) | ||||||
UniProt | A0S864 | ||||||
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Irdixotin subunit B | |||||||
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Identifiers | |||||||
Organism | |||||||
Symbol | 3NBB | ||||||
PDB | 2H7Z (ECOD) | ||||||
UniProt | A0S865 | ||||||
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Irditoxin is a three-finger toxin (3FTx) protein found in the venom of the brown tree snake (Boiga irregularis) and likely in other members of the genus Boiga. It is a heterodimer composed of two distinct protein chains, each of the three-finger protein fold, linked by an intermolecular disulfide bond. This structure is unusual for 3FTx proteins, which are most commonly monomeric.[1][2][3]
Structure
Three-finger toxin (3FTx) proteins canonically consist of approximately 60-80 amino acid residues that assume a structure with three "finger"-like beta strand-containing loops projecting from a core stabilized by four intramolecular disulfide bonds. Irditoxin is a covalent heterodimer in which two subunits are linked by an intermolecular disulfide bond. Each subunit is of the three-finger toxin (3FTx) protein superfamily and is most closely related to the "non-conventional" 3FTx subclass, characterized by the presence of an additional disulfide bond in the first of the canonical three "finger" loops. Each subunit thus contains 11 cysteine residues: the eight canonical residues that form the core disulfide bonds, the two in the first loop forming the non-conventional disulfide, and the one that forms the dimeric linkage. Irditoxin subunits A and B are 75 and 77 amino acid residues long, respectively, and each possess a seven-residue extension with a pyroglutamic acid post-translational modification at the N-terminus.[1][2]
Irditoxin's structure is highly unusual within the 3FTx superfamily.[2] Most 3FTx proteins are monomers. The best-studied exception is kappa-bungarotoxin, a non-covalent homodimer with a very different protein-protein interaction surface;[2] the recently described alpha-cobratoxin also forms both covalent homodimers and low-abundance covalent heterodimers with other 3FTx proteins found in monocled cobra (Naja kaouthia) venom.[4] It is as yet unclear how irditoxin's two subunits contribute to its biological activities.[2]
Function
Irditoxin is an abundant protein in the venom of the brown tree snake and accounts for about 10% of the protein found in venom samples of brown treesnakes collected from Guam, where they are an invasive species. Irditoxin's toxic effects are highly species-dependent; in laboratory tests, it is highly toxic to lizards and birds but not to mammals. Although the molecular mechanism of toxicity is not clear, irditoxin produces robust post-synaptic blockade of signaling in the avian neuromuscular junction.[1]
Discovery and nomenclature
Irditoxin was first described in 2009 after isolation from samples of venom from the brown tree snake. Its name is a contraction of "B. irregularis dimeric toxin".[1] Other Boiga species, and possibly other colubrid snakes, likely possess homologous proteins.[5]:18
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity". FASEB Journal 23 (2): 534–45. February 2009. doi:10.1096/fj.08-113555. PMID 18952712. http://www.fasebj.org/content/23/2/534.
- ↑ 2.0 2.1 2.2 2.3 2.4 "Structure, function and evolution of three-finger toxins: mini proteins with multiple targets". Toxicon 56 (6): 855–67. November 2010. doi:10.1016/j.toxicon.2010.07.010. PMID 20670641.
- ↑ "Protein complexes in snake venom". Cellular and Molecular Life Sciences 66 (17): 2851–71. September 2009. doi:10.1007/s00018-009-0050-2. PMID 19495561.
- ↑ "Dimeric α-cobratoxin X-ray structure: localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors". The Journal of Biological Chemistry 287 (9): 6725–34. February 2012. doi:10.1074/jbc.M111.322313. PMID 22223648.
- ↑ Mackessy, Stephen P. (2010-01-01). Handbook of venoms and toxins of reptiles. CRC Press. ISBN 9781420008661. OCLC 757355711.
Original source: https://en.wikipedia.org/wiki/Irditoxin.
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