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The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3
Choanoflagellates are primitive protozoa used as models for animal evolution. They express a large variety of multi-domain proteins contributing to adhesion and cell communication, thereby providing a rich repertoire of molecules for biotechnology. Adhesion often involves proteins adopting a β-trefo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468336/ https://www.ncbi.nlm.nih.gov/pubmed/36097056 http://dx.doi.org/10.1038/s42003-022-03869-w |
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author | Notova, Simona Bonnardel , François Rosato, Francesca Siukstaite, Lina Schwaiger, Jessica Lim, Jia Hui Bovin, Nicolai Varrot, Annabelle Ogawa, Yu Römer, Winfried Lisacek, Frédérique Imberty, Anne |
author_facet | Notova, Simona Bonnardel , François Rosato, Francesca Siukstaite, Lina Schwaiger, Jessica Lim, Jia Hui Bovin, Nicolai Varrot, Annabelle Ogawa, Yu Römer, Winfried Lisacek, Frédérique Imberty, Anne |
author_sort | Notova, Simona |
collection | PubMed |
description | Choanoflagellates are primitive protozoa used as models for animal evolution. They express a large variety of multi-domain proteins contributing to adhesion and cell communication, thereby providing a rich repertoire of molecules for biotechnology. Adhesion often involves proteins adopting a β-trefoil fold with carbohydrate-binding properties therefore classified as lectins. Sequence database screening with a dedicated method resulted in TrefLec, a database of 44714 β-trefoil candidate lectins across 4497 species. TrefLec was searched for original domain combinations, which led to single out SaroL-1 in the choanoflagellate Salpingoeca rosetta, that contains both β-trefoil and aerolysin-like pore-forming domains. Recombinant SaroL-1 is shown to bind galactose and derivatives, with a stronger affinity for cancer-related α-galactosylated epitopes such as the glycosphingolipid Gb3, when embedded in giant unilamellar vesicles or cell membranes. Crystal structures of complexes with Gb3 trisaccharide and GalNAc provided the basis for building a model of the oligomeric pore. Finally, recognition of the αGal epitope on glycolipids required for hemolysis of rabbit erythrocytes suggests that toxicity on cancer cells is achieved through carbohydrate-dependent pore-formation. |
format | Online Article Text |
id | pubmed-9468336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94683362022-09-14 The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 Notova, Simona Bonnardel , François Rosato, Francesca Siukstaite, Lina Schwaiger, Jessica Lim, Jia Hui Bovin, Nicolai Varrot, Annabelle Ogawa, Yu Römer, Winfried Lisacek, Frédérique Imberty, Anne Commun Biol Article Choanoflagellates are primitive protozoa used as models for animal evolution. They express a large variety of multi-domain proteins contributing to adhesion and cell communication, thereby providing a rich repertoire of molecules for biotechnology. Adhesion often involves proteins adopting a β-trefoil fold with carbohydrate-binding properties therefore classified as lectins. Sequence database screening with a dedicated method resulted in TrefLec, a database of 44714 β-trefoil candidate lectins across 4497 species. TrefLec was searched for original domain combinations, which led to single out SaroL-1 in the choanoflagellate Salpingoeca rosetta, that contains both β-trefoil and aerolysin-like pore-forming domains. Recombinant SaroL-1 is shown to bind galactose and derivatives, with a stronger affinity for cancer-related α-galactosylated epitopes such as the glycosphingolipid Gb3, when embedded in giant unilamellar vesicles or cell membranes. Crystal structures of complexes with Gb3 trisaccharide and GalNAc provided the basis for building a model of the oligomeric pore. Finally, recognition of the αGal epitope on glycolipids required for hemolysis of rabbit erythrocytes suggests that toxicity on cancer cells is achieved through carbohydrate-dependent pore-formation. Nature Publishing Group UK 2022-09-12 /pmc/articles/PMC9468336/ /pubmed/36097056 http://dx.doi.org/10.1038/s42003-022-03869-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Notova, Simona Bonnardel , François Rosato, Francesca Siukstaite, Lina Schwaiger, Jessica Lim, Jia Hui Bovin, Nicolai Varrot, Annabelle Ogawa, Yu Römer, Winfried Lisacek, Frédérique Imberty, Anne The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title | The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title_full | The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title_fullStr | The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title_full_unstemmed | The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title_short | The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3 |
title_sort | choanoflagellate pore-forming lectin sarol-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid gb3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468336/ https://www.ncbi.nlm.nih.gov/pubmed/36097056 http://dx.doi.org/10.1038/s42003-022-03869-w |
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