Structural insights into wasp venom: Small molecules, peptides, and proteins

Wasp venom is a structurally complex secretion composed of small molecules, peptides, and proteins that fulfil distinct biological roles. This review provides a comprehensive overview of wasp venom constituents, with particular emphasis on the structural diversity of peptides and proteins. Small molecules such as biogenic amines, free amino acids, and volatile compounds contribute to venom toxicity but exhibit limited structural complexity. In contrast, venom peptides, including neurotoxins, kinins, mastoparans, and chemotactic peptides, display diverse amino acid compositions, amphipathic architectures, and characteristic charge distributions. Most peptides are intrinsically disordered in aqueous solution but adopt defined secondary structures, predominantly α-helices or β-turns, in complex with G-proteins and in membrane-mimetic environments, with conformational properties strongly influenced by lipid composition, C-terminal modifications, and conserved sequence motifs. Larger venom proteins, such as phospholipases, hyaluronidases, and antigen 5, exhibit distinct domain architectures and stabilising features, including disulfide bonds and oligomerisation, that underpin their enzymatic activity and allergenicity. By integrating functional and experimentally determined structural data across major molecular classes, this review highlights the remarkable molecular diversity of wasp venom and underscores the need for continued structural characterisation of its many still poorly understood components, particularly in the context of their biomedical and therapeutic potential.