Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.

Thioester-containing protein 1 (TEP1) is a central component in the innate immune response of Anopheles gambiae to Plasmodium infection. Two classes of TEP1 alleles, TEP1*S and TEP1*R, are found in both laboratory strains and wild isolates, related by a greater or lesser susceptibility, respectively...

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Autores principales:	Binh V Le, Marni Williams, Shankar Logarajah, Richard H G Baxter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bc1165de1ec24960b6c0b3c2d8133522
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spelling	oai:doaj.org-article:bc1165de1ec24960b6c0b3c2d81335222021-11-18T06:06:29ZMolecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.1553-73661553-737410.1371/journal.ppat.1002958https://doaj.org/article/bc1165de1ec24960b6c0b3c2d81335222012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23055931/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Thioester-containing protein 1 (TEP1) is a central component in the innate immune response of Anopheles gambiae to Plasmodium infection. Two classes of TEP1 alleles, TEP1S and TEP1R, are found in both laboratory strains and wild isolates, related by a greater or lesser susceptibility, respectively to both P. berghei and P. falciparum infection. We report the crystal structure of the full-length TEP1S1 allele which, while similar to the previously determined structure of full-length TEP1R1, displays flexibility in the N-terminal fragment comprising domains MG1-MG6. Amino acid differences between TEP1R1 and TEP1S1 are localized to the TED-MG8 domain interface that protects the thioester bond from hydrolysis and structural changes are apparent at this interface. As a consequence cleaved TEP1S1 (TEP1S1(cut)) is significantly more susceptible to hydrolysis of its intramolecular thioester bond than TEP1R1(cut). TEP1S1(cut) is stabilized in solution by the heterodimeric LRIM1/APL1C complex, which preserves the thioester bond within TEP1*S1(cut). These results suggest a mechanism by which selective pressure on the TEP1 gene results in functional variation that may influence the vector competence of A. gambiae towards Plasmodium infection.Binh V LeMarni WilliamsShankar LogarajahRichard H G BaxterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 10, p e1002958 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Binh V Le Marni Williams Shankar Logarajah Richard H G Baxter Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
description	Thioester-containing protein 1 (TEP1) is a central component in the innate immune response of Anopheles gambiae to Plasmodium infection. Two classes of TEP1 alleles, TEP1S and TEP1R, are found in both laboratory strains and wild isolates, related by a greater or lesser susceptibility, respectively to both P. berghei and P. falciparum infection. We report the crystal structure of the full-length TEP1S1 allele which, while similar to the previously determined structure of full-length TEP1R1, displays flexibility in the N-terminal fragment comprising domains MG1-MG6. Amino acid differences between TEP1R1 and TEP1S1 are localized to the TED-MG8 domain interface that protects the thioester bond from hydrolysis and structural changes are apparent at this interface. As a consequence cleaved TEP1S1 (TEP1S1(cut)) is significantly more susceptible to hydrolysis of its intramolecular thioester bond than TEP1R1(cut). TEP1S1(cut) is stabilized in solution by the heterodimeric LRIM1/APL1C complex, which preserves the thioester bond within TEP1*S1(cut). These results suggest a mechanism by which selective pressure on the TEP1 gene results in functional variation that may influence the vector competence of A. gambiae towards Plasmodium infection.
format	article
author	Binh V Le Marni Williams Shankar Logarajah Richard H G Baxter
author_facet	Binh V Le Marni Williams Shankar Logarajah Richard H G Baxter
author_sort	Binh V Le
title	Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
title_short	Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
title_full	Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
title_fullStr	Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
title_full_unstemmed	Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.
title_sort	molecular basis for genetic resistance of anopheles gambiae to plasmodium: structural analysis of tep1 susceptible and resistant alleles.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/bc1165de1ec24960b6c0b3c2d8133522
work_keys_str_mv	AT binhvle molecularbasisforgeneticresistanceofanophelesgambiaetoplasmodiumstructuralanalysisoftep1susceptibleandresistantalleles AT marniwilliams molecularbasisforgeneticresistanceofanophelesgambiaetoplasmodiumstructuralanalysisoftep1susceptibleandresistantalleles AT shankarlogarajah molecularbasisforgeneticresistanceofanophelesgambiaetoplasmodiumstructuralanalysisoftep1susceptibleandresistantalleles AT richardhgbaxter molecularbasisforgeneticresistanceofanophelesgambiaetoplasmodiumstructuralanalysisoftep1susceptibleandresistantalleles
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Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles.

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