Irditoxin is a

three-finger toxin Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic prote ...

(3FTx)

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

found in the

venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

of the

brown tree snake The brown tree snake (''Boiga irregularis''), also known as the brown catsnake, is an arboreal rear-fanged colubrid snake native to eastern and northern coastal Australia, eastern Indonesia (Sulawesi to Papua), Papua New Guinea, and many islands ...

(''Boiga irregularis'') and likely in other members of the

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...

Boiga ''Boiga'' is a large genus of rear-fanged, mildly venomous snakes, known commonly as cat-eyed snakes or simply cat snakes, in the family Colubridae. Species of the genus ''Boiga'' are native to southeast Asia, India, and Australia, but due to ...

''. It is a

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

composed of two distinct protein chains, each of the three-finger protein fold, linked by an intermolecular

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...

. This structure is unusual for 3FTx proteins, which are most commonly monomeric.

Structure

Three-finger toxin Three-finger toxins (abbreviated 3FTx) are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic prote ...

(3FTx) proteins canonically consist of approximately 60-80

amino acid residue Protein structure is the molecular geometry, three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single ami ...

s that assume a structure with three "finger"-like

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

-containing loops projecting from a core stabilized by four intramolecular disulfide bonds. Irditoxin is a

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

in which two subunits are linked by an intermolecular

. Each subunit is of the

(3FTx)

protein superfamily A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology (biology), homology). Usually this common ancestry is inferred from structural alignment and mechanistic similarity, even if n ...

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 Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

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

s long, respectively, and each possess a seven-residue extension with a

pyroglutamic acid Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but little studied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam. The names of pyroglutamic ac ...

post-translational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

at the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

. Irditoxin's structure is highly unusual within the 3FTx superfamily. Most 3FTx proteins are monomers. The best-studied exception is kappa-bungarotoxin, a non-covalent homodimer with a very different protein-protein interaction surface; the recently described alpha-cobratoxin also forms both covalent homodimers and low-abundance covalent heterodimers with other 3FTx proteins found in

monocled cobra The monocled cobra (''Naja kaouthia''), also called monocellate cobra and Indian spitting cobra, is a venomous cobra species widespread across South and Southeast Asia and listed as Least Concern on the IUCN Red List. Taxonomy The scientific n ...

(''Naja kaouthia'') venom. It is as yet unclear how irditoxin's two subunits contribute to its biological activities.

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 Guam (; ch, Guåhan ) is an organized, unincorporated territory of the United States in the Micronesia subregion of the western Pacific Ocean. It is the westernmost point and territory of the United States (reckoned from the geographic cent ...

, where they are an

invasive species An invasive species otherwise known as an alien is an introduced organism that becomes overpopulated and harms its new environment. Although most introduced species are neutral or beneficial with respect to other species, invasive species ad ...

. Irditoxin's toxic effects are highly species-dependent; in laboratory tests, it is highly toxic to

lizard Lizards are a widespread group of squamate reptiles, with over 7,000 species, ranging across all continents except Antarctica, as well as most oceanic island chains. The group is paraphyletic since it excludes the snakes and Amphisbaenia alt ...

s and

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...

s but not to

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

s. Although the molecular mechanism of toxicity is not clear, irditoxin produces robust post- synaptic blockade of signaling in the avian

neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

Discovery and nomenclature

Irditoxin was first described in 2009 after isolation from samples of venom from the

. Its name is a contraction of "''B. irregularis'' dimeric toxin". Other ''

'' species, and possibly other

colubrid Colubridae (, commonly known as colubrids , from la, coluber, 'snake') is a family of snakes. With 249 genera, it is the largest snake family. The earliest species of the family date back to the Oligocene epoch. Colubrid snakes are found on ever ...

snakes, likely possess homologous proteins.

References

{{reflist, 32em Neurotoxins