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

GIGLIO, MATÍAS; ITUARTE, SANTIAGO; MILESI, VERÓNICA ; DREON, MARCOS; BROLA, TABATA; CARAMELO, JULIO; IP, JACK; MATÉ, SABINA; QIU, JIAN-WEN ; OTERO, LISANDRO HORACIO *; HERAS, HORACIO* (* CORRESPONDING AUTHORS) (ARTÍCULO SELECCIONADO TAPA DE REVISTA)

JOURNAL OF STRUCTURAL BIOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2020 vol. 211

1047-8477

The Membrane AttackComplex-Perforin (MACPF) family is ubiquitously found in allkingdoms. They have diverse cellular roles, however MACPFs withpore-forming toxic function in venoms and poisons are very rare inanimals. Here we present the structure of PmPV2, a MACPF toxin fromthe poisonous apple snail eggs, that can affect the digestive andnervous systems of potential predators. We report thethree-dimensional structure of PmPV2, at 17.2 Å resolutiondetermined by negative-stain electron microscopy and its solutionstructure by small angle X-ray scattering (SAXS). We found that PV2sdiffer from nearly all MACPFs in two respects: it is a dimer insolution and protomers combine two immune proteins into an AB toxin.The MACPF chain is linked by a single disulfide bond to a tachylectinchain, and two heterodimers are arranged head-to-tail by non-covalentforces in the native protein. MACPF domain is fused with a putativenew Ct-accessory domain exclusive to invertebrates. The tachylectinis a six-bladed β-propeller, similar to animal tectonins. Weexperimentally validated the predicted functions of both subunits anddemonstrated for the first time that PV2s are true pore-formingtoxins. The tachylectin ?B? delivery subunit would bind to targetmembranes, and then the MACPF ?A? toxic subunit would disruptlipid bilayers forming large pores altering the plasma membraneconductance. These results indicate that PV2s toxicity evolved bylinking two immune proteins where their combined preexisting functions gave riseto a new toxic entity with a novel role in defense against predation.This structure is an unparalleled example of protein exaptation.