Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails

M. L. Giglio, S. Ituarte, V. Milesi, M. S. Dreon, T. R. Brola, J. Caramelo, Jack Chi Ho Ip, S. Maté, Jianwen Qiu, L. H. Otero*, H. Heras*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

5 Citations (Scopus)


The Membrane Attack Complex-Perforin (MACPF) family is ubiquitously found in all kingdoms. They have diverse cellular roles, however MACPFs with pore-forming toxic function in venoms and poisons are very rare in animals. Here we present the structure of PmPV2, a MACPF toxin from the poisonous apple snail eggs, that can affect the digestive and nervous systems of potential predators. We report the three-dimensional structure of PmPV2, at 17.2 Å resolution determined by negative-stain electron microscopy and its solution structure by small angle X-ray scattering (SAXS). We found that PV2s differ from nearly all MACPFs in two respects: it is a dimer in solution and protomers combine two immune proteins into an AB toxin. The MACPF chain is linked by a single disulfide bond to a tachylectin chain, and two heterodimers are arranged head-to-tail by non-covalent forces in the native protein. MACPF domain is fused with a putative new Ct-accessory domain exclusive to invertebrates. The tachylectin is a six-bladed β-propeller, similar to animal tectonins. We experimentally validated the predicted functions of both subunits and demonstrated for the first time that PV2s are true pore-forming toxins. The tachylectin “B” delivery subunit would bind to target membranes, and then the MACPF “A” toxic subunit would disrupt lipid bilayers forming large pores altering the plasma membrane conductance. These results indicate that PV2s toxicity evolved by linking two immune proteins where their combined preexisting functions gave rise to a new toxic entity with a novel role in defense against predation. This structure is an unparalleled example of protein exaptation.

Original languageEnglish
Article number107531
Number of pages11
JournalJournal of Structural Biology
Issue number2
Publication statusPublished - 1 Aug 2020

Scopus Subject Areas

  • Structural Biology

User-Defined Keywords

  • AB toxin
  • Lectin
  • Poisonous egg defense
  • Pomacea


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