Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP
Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin αβ heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxopl...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/57572 |
| _version_ | 1811253275585937408 |
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| author | Dennis Klug Sarah Goellner Jessica Kehrer Julia Sattler Léanne Strauss Mirko Singer Chafen Lu Timothy A Springer Friedrich Frischknecht |
| author_facet | Dennis Klug Sarah Goellner Jessica Kehrer Julia Sattler Léanne Strauss Mirko Singer Chafen Lu Timothy A Springer Friedrich Frischknecht |
| author_sort | Dennis Klug |
| collection | DOAJ |
| description | Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin αβ heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aX I domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla. |
| first_indexed | 2024-04-12T16:48:28Z |
| format | Article |
| id | doaj.art-d586dc10aeb04760852dd197df2c9446 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:48:28Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d586dc10aeb04760852dd197df2c94462022-12-22T03:24:30ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.57572Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAPDennis Klug0https://orcid.org/0000-0002-9108-454XSarah Goellner1https://orcid.org/0000-0002-3300-4273Jessica Kehrer2https://orcid.org/0000-0001-5084-3485Julia Sattler3Léanne Strauss4https://orcid.org/0000-0002-0680-593XMirko Singer5https://orcid.org/0000-0002-5757-2750Chafen Lu6Timothy A Springer7https://orcid.org/0000-0001-6627-2904Friedrich Frischknecht8https://orcid.org/0000-0002-8332-6668Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Université de Strasbourg, CNRS UPR9022, INSERM U963, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, FranceIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Department of Molecular Virology, Heidelberg University Medical School, Heidelberg, GermanyIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, GermanyIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, GermanyIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, GermanyIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, Germany; Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, München, GermanyProgram in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, United StatesProgram in Cellular and Molecular Medicine, Children's Hospital Boston, and Departments of Biological Chemistry and Molecular Pharmacology and of Medicine, Harvard Medical School, Boston, United StatesIntegrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Heidelberg, GermanyInserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin αβ heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aX I domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla.https://elifesciences.org/articles/57572Plasmodium bergheimalariamotilityinvasionintegrinadhesion |
| spellingShingle | Dennis Klug Sarah Goellner Jessica Kehrer Julia Sattler Léanne Strauss Mirko Singer Chafen Lu Timothy A Springer Friedrich Frischknecht Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP eLife Plasmodium berghei malaria motility invasion integrin adhesion |
| title | Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP |
| title_full | Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP |
| title_fullStr | Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP |
| title_full_unstemmed | Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP |
| title_short | Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP |
| title_sort | evolutionarily distant i domains can functionally replace the essential ligand binding domain of plasmodium trap |
| topic | Plasmodium berghei malaria motility invasion integrin adhesion |
| url | https://elifesciences.org/articles/57572 |
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