Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin
The perivitellin-2 (PV2) from snails is an unusual neuro and enterotoxin comprising a pore-forming domain of the Membrane Attack Complex and Perforin Family (MACPF) linked to a lectin. While both domains have membrane binding capabilities, PV2’s mechanism of action remains unclear. We studied the ap...
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MDPI AG
2025-04-01
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| author | Romina F. Vázquez M. Antonieta Daza Millone Matías L. Giglio Tabata R. Brola Sabina M. Maté Horacio Heras |
| author_facet | Romina F. Vázquez M. Antonieta Daza Millone Matías L. Giglio Tabata R. Brola Sabina M. Maté Horacio Heras |
| author_sort | Romina F. Vázquez |
| collection | DOAJ |
| description | The perivitellin-2 (PV2) from snails is an unusual neuro and enterotoxin comprising a pore-forming domain of the Membrane Attack Complex and Perforin Family (MACPF) linked to a lectin. While both domains have membrane binding capabilities, PV2’s mechanism of action remains unclear. We studied the apple snail <i>Pomacea maculata</i> PV2’s (PmPV2’s) interaction with lipid membranes using various biophysical and cell biology approaches. In vitro studies showed that PmPV2 toxicity decreased when cholesterol (Chol) was diminished from enterocyte cell membranes. Chol enhanced PmPV2 association with phosphatidylcholine membranes but did not induce pore formation. In contrast, using rat brain lipid models, rich in glycolipids, PmPV2 exhibited high affinity and induced vesicle permeabilization. Negative stain electron microscopy and atomic force microscopy confirmed the formation of pore-like structures in brain lipid vesicles. Our findings suggest that Chol is a necessary lipid component and point to PmPV2–glycolipid interactions as potential activators critical to triggering PmPV2’s pore-forming activity, providing insights into this novel toxin’s mechanism. |
| format | Article |
| id | doaj-art-18f97bda7d1941b1a036733346706795 |
| institution | OA Journals |
| issn | 2072-6651 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj-art-18f97bda7d1941b1a0367333467067952025-08-20T02:18:10ZengMDPI AGToxins2072-66512025-04-0117418310.3390/toxins17040183Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming ToxinRomina F. Vázquez0M. Antonieta Daza Millone1Matías L. Giglio2Tabata R. Brola3Sabina M. Maté4Horacio Heras5Instituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner”, INIBIOLP, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata 1900, ArgentinaInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas, INIFTA, CCT-La Plata, CONICET, Universidad Nacional de La Plata, Diagonal 113 y 64, La Plata 1900, ArgentinaInstituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner”, INIBIOLP, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata 1900, ArgentinaInstituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner”, INIBIOLP, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata 1900, ArgentinaInstituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner”, INIBIOLP, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata 1900, ArgentinaInstituto de Investigaciones Bioquímicas de La Plata “Prof. Dr. Rodolfo R. Brenner”, INIBIOLP, CCT-La Plata, CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata 1900, ArgentinaThe perivitellin-2 (PV2) from snails is an unusual neuro and enterotoxin comprising a pore-forming domain of the Membrane Attack Complex and Perforin Family (MACPF) linked to a lectin. While both domains have membrane binding capabilities, PV2’s mechanism of action remains unclear. We studied the apple snail <i>Pomacea maculata</i> PV2’s (PmPV2’s) interaction with lipid membranes using various biophysical and cell biology approaches. In vitro studies showed that PmPV2 toxicity decreased when cholesterol (Chol) was diminished from enterocyte cell membranes. Chol enhanced PmPV2 association with phosphatidylcholine membranes but did not induce pore formation. In contrast, using rat brain lipid models, rich in glycolipids, PmPV2 exhibited high affinity and induced vesicle permeabilization. Negative stain electron microscopy and atomic force microscopy confirmed the formation of pore-like structures in brain lipid vesicles. Our findings suggest that Chol is a necessary lipid component and point to PmPV2–glycolipid interactions as potential activators critical to triggering PmPV2’s pore-forming activity, providing insights into this novel toxin’s mechanism.https://www.mdpi.com/2072-6651/17/4/183MACPFsnail pore-forming toxinneurotoxin/enterotoxinlectinlipid membranesprotein–lipid interaction |
| spellingShingle | Romina F. Vázquez M. Antonieta Daza Millone Matías L. Giglio Tabata R. Brola Sabina M. Maté Horacio Heras Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin Toxins MACPF snail pore-forming toxin neurotoxin/enterotoxin lectin lipid membranes protein–lipid interaction |
| title | Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin |
| title_full | Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin |
| title_fullStr | Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin |
| title_full_unstemmed | Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin |
| title_short | Insights into the Protein–Lipid Interaction of Perivitellin-2, an Unusual Snail Pore-Forming Toxin |
| title_sort | insights into the protein lipid interaction of perivitellin 2 an unusual snail pore forming toxin |
| topic | MACPF snail pore-forming toxin neurotoxin/enterotoxin lectin lipid membranes protein–lipid interaction |
| url | https://www.mdpi.com/2072-6651/17/4/183 |
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