Artículo
Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
Giglio, Matías Leonel
; Ituarte, Santiago
; Milesi, Verónica
; Dreon, Marcos Sebastian
; Brola, Tabata Romina
; Caramelo, Julio Javier
; Ip, Jack Chi Ho; Maté, Sabina María
; Qiu, Jian Wen; Otero, Lisandro Horacio
; Heras, Horacio
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Fecha de publicación:
01/08/2020
Editorial:
Academic Press Inc Elsevier Science
Revista:
Journal Of Structural Biology
ISSN:
1047-8477
e-ISSN:
1095-8657
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
AB TOXIN
,
LECTIN
,
MACPF
,
POISONOUS EGG DEFENSE
,
POMACEA
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Giglio, Matías Leonel; Ituarte, Santiago; Milesi, Verónica; Dreon, Marcos Sebastian; Brola, Tabata Romina; et al.; Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails; Academic Press Inc Elsevier Science; Journal Of Structural Biology; 211; 2; 1-8-2020; 1-11
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