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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Giglio, Matías Leonel, Ituarte, Santiago, Milesi, María Verónica, Dreon, Marcos Sebastián, Brola, Tabata Romina, Caramelo, Julio J., Ip, Jack C.H., Maté, Sabina María, Qiu, Jian-Wen, Otero, Lisandro H., Heras, Horacio
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2020
Materias:
Bioquímica
Pore-forming toxin
Poisonous snail egg
PmPV2
Lectin
AB toxin,
Pomacea
Chemical defense
Negative stain electron microscopy
Small-angle X-ray scattering
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127974
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-127974
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Pore-forming toxin
Poisonous snail egg
PmPV2
Lectin
AB toxin,
Pomacea
Chemical defense
Negative stain electron microscopy
Small-angle X-ray scattering
spellingShingle Bioquímica
Pore-forming toxin
Poisonous snail egg
PmPV2
Lectin
AB toxin,
Pomacea
Chemical defense
Negative stain electron microscopy
Small-angle X-ray scattering
Giglio, Matías Leonel
Ituarte, Santiago
Milesi, María Verónica
Dreon, Marcos Sebastián
Brola, Tabata Romina
Caramelo, Julio J.
Ip, Jack C.H.
Maté, Sabina María
Qiu, Jian-Wen
Otero, Lisandro H.
Heras, Horacio
Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
topic_facet Bioquímica
Pore-forming toxin
Poisonous snail egg
PmPV2
Lectin
AB toxin,
Pomacea
Chemical defense
Negative stain electron microscopy
Small-angle X-ray scattering
description 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 A 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.
format Articulo
Preprint
author Giglio, Matías Leonel
Ituarte, Santiago
Milesi, María Verónica
Dreon, Marcos Sebastián
Brola, Tabata Romina
Caramelo, Julio J.
Ip, Jack C.H.
Maté, Sabina María
Qiu, Jian-Wen
Otero, Lisandro H.
Heras, Horacio
author_facet Giglio, Matías Leonel
Ituarte, Santiago
Milesi, María Verónica
Dreon, Marcos Sebastián
Brola, Tabata Romina
Caramelo, Julio J.
Ip, Jack C.H.
Maté, Sabina María
Qiu, Jian-Wen
Otero, Lisandro H.
Heras, Horacio
author_sort Giglio, Matías Leonel
title Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
title_short Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
title_full Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
title_fullStr Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
title_full_unstemmed Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
title_sort exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/127974
work_keys_str_mv AT gigliomatiasleonel exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT ituartesantiago exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT milesimariaveronica exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT dreonmarcossebastian exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT brolatabataromina exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT caramelojulioj exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT ipjackch exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT matesabinamaria exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT qiujianwen exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT oterolisandroh exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
AT herashoracio exaptationoftwoancientimmuneproteinsintoanewdimericporeformingtoxininsnails
bdutipo_str Repositorios
_version_ 1764820451600629761

Ejemplares similares