Ptu1 is a

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

that can reversibly bind

N-type calcium channel N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the prima ...

s. It is isolated from the

assassin bug The Reduviidae are a large cosmopolitan family of the order Hemiptera (true bugs). Among the Hemiptera and together with the Nabidae almost all species are terrestrial ambush predators: most other predatory Hemiptera are aquatic. The main exampl ...

''Peirates turpis''. The toxin belongs to the inhibitory cystine knot structural family (ICK) that has a core of

disulfide 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 ...

bonds with four loops emerging from it.

Etymology and source

Ptu1 is named after the bug ''Peirates turpis'', where it is found. The peptide is found in its saliva.

Chemistry and targets

Ptu1 is a relatively short peptide of around 3.6 kDa. Its structure belongs to the inhibitory cystine knot family. This is a structural motif that contains at least three disulfide bridges, from which several loops may emerge. The knot is formed by having one disulfide bridge cross the other two disulfide bridges. Disulfide bridges are made by forming a cysteine dimer, called cystine. Due to this, it has a high disulfide content, making ICK motifs highly stable. In line with this, Ptu1 consists of a core of compact disulfide bonds. From this core a total of four loops emerge, along with its C- and N-termini The structure of Ptu1 is slightly homologous with the ω-

conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Cono ...

s.: Geographus Venom IA (GVIA) and Mollusc Venom IIA (MVIIA). They both share the inhibitor cystine knot motif. Their structure is 17% and 23% homologous, respectively Besides the ICK motif, the toxin contains a

β-sheet 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 ...

made of two β-strands in an antiparallel orientation. The molecule may exist in two conformations, between which it rapidly switches Ptu1 binds reversibly to voltage gated

Mode of action

Ptu1 reversibly blocks

s. In addition, it has a low affinity for L or P/Q-type channels. The mechanism by which Ptu1 blocks N-type voltage dependent calcium channels is unknown. Since it has a structural similarity to the ω-

s, it is possible that their blocking mechanism is similar. MVIIA is a pore-blocking toxin. There are two key differences between the functionality of MVIIA and Ptu1. First, the binding of MVIIA is irreversible, whereas the binding of Ptu1 is reversible. Second, Ptu1 has a relatively low binding affinity for N-type calcium channels compared to MVIIA. A possible explanation for this difference is the presence of an aspartic acid residue in the second loop of Ptu1

Toxicity

The toxicity of Ptu1 was tested by direct injection into the body of goldfish, mice, cutworm larvae, and crickets. The assassin bug peptide showed no toxic symptoms in any of the tested vertebrates and invertebrates.

References

{{reflist Insect toxins Peripheral membrane proteins