NDLI: Molecular Basis for Genetic Resistance of Anopheles gambiae to Plasmodium: Structural Analysis of TEP1 Susceptible and Resistant Alleles

Content Provider	PubMed Central
Author	Le, Binh V. Williams, Marni Shankar, Logarajah Baxter, Richard H. G.
Editor	Vernick, Kenneth D.
Copyright Year	2012
Abstract	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 (TEP1S1cut) is significantly more susceptible to hydrolysis of its intramolecular thioester bond than TEP1R1cut. TEP1S1cut is stabilized in solution by the heterodimeric LRIM1/APL1C complex, which preserves the thioester bond within TEP1*S1cut. 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.
Related Links	http://dx.doi.org/10.1371/journal.ppat.1002958
Starting Page	1002958
File Format	PDF
ISSN	15537374
e-ISSN	15537374
Journal	PLoS Pathogens
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2012-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Immunology Genetics Molecular Biology Microbiology Parasitology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Virology Molecular Biology Parasitology Immunology Microbiology

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