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Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6
The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting f...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605323/ https://www.ncbi.nlm.nih.gov/pubmed/34753804 http://dx.doi.org/10.26508/lsa.202101149 |
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author | Saijo-Hamano, Yumiko Sherif, Aalaa Alrahman Pradipta, Ariel Sasai, Miwa Sakai, Naoki Sakihama, Yoshiaki Yamamoto, Masahiro Standley, Daron M Nitta, Ryo |
author_facet | Saijo-Hamano, Yumiko Sherif, Aalaa Alrahman Pradipta, Ariel Sasai, Miwa Sakai, Naoki Sakihama, Yoshiaki Yamamoto, Masahiro Standley, Daron M Nitta, Ryo |
author_sort | Saijo-Hamano, Yumiko |
collection | PubMed |
description | The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs. |
format | Online Article Text |
id | pubmed-8605323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-86053232021-12-02 Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 Saijo-Hamano, Yumiko Sherif, Aalaa Alrahman Pradipta, Ariel Sasai, Miwa Sakai, Naoki Sakihama, Yoshiaki Yamamoto, Masahiro Standley, Daron M Nitta, Ryo Life Sci Alliance Research Articles The p47 immunity-related GTPase (IRG) Irgb6 plays a pioneering role in host defense against Toxoplasma gondii infection. Irgb6 is recruited to the parasitophorous vacuole membrane (PVM) formed by T. gondii and disrupts it. Despite the importance of this process, the molecular mechanisms accounting for PVM recognition by Irgb6 remain elusive because of lack of structural information on Irgb6. Here we report the crystal structures of mouse Irgb6 in the GTP-bound and nucleotide-free forms. Irgb6 exhibits a similar overall architecture to other IRGs in which GTP binding induces conformational changes in both the dimerization interface and the membrane-binding interface. The membrane-binding interface of Irgb6 assumes a unique conformation, composed of N- and C-terminal helical regions forming a phospholipid binding site. In silico docking of phospholipids further revealed membrane-binding residues that were validated through mutagenesis and cell-based assays. Collectively, these data demonstrate a novel structural basis for Irgb6 to recognize T. gondii PVM in a manner distinct from other IRGs. Life Science Alliance LLC 2021-11-09 /pmc/articles/PMC8605323/ /pubmed/34753804 http://dx.doi.org/10.26508/lsa.202101149 Text en © 2021 Saijo-Hamano et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Saijo-Hamano, Yumiko Sherif, Aalaa Alrahman Pradipta, Ariel Sasai, Miwa Sakai, Naoki Sakihama, Yoshiaki Yamamoto, Masahiro Standley, Daron M Nitta, Ryo Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title | Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title_full | Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title_fullStr | Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title_full_unstemmed | Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title_short | Structural basis of membrane recognition of Toxoplasma gondii vacuole by Irgb6 |
title_sort | structural basis of membrane recognition of toxoplasma gondii vacuole by irgb6 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605323/ https://www.ncbi.nlm.nih.gov/pubmed/34753804 http://dx.doi.org/10.26508/lsa.202101149 |
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