Summary for 4LNV
Entry DOI | 10.2210/pdb4lnv/pdb |
Related | 4D94 |
Descriptor | Thioester-containing protein I, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
Functional Keywords | immune system, innate immunity, lrim1 and apl1c |
Biological source | Anopheles gambiae (African malaria mosquito) |
Total number of polymer chains | 3 |
Total formula weight | 455823.30 |
Authors | Le, B.V.,Williams, M.,Logarajah, S.,Baxter, R.H.G. (deposition date: 2013-07-12, release date: 2013-07-24, Last modification date: 2024-10-30) |
Primary citation | Le, B.V.,Williams, M.,Logarajah, S.,Baxter, R.H. Molecular basis for genetic resistance of Anopheles gambiae to Plasmodium: structural analysis of TEP1 susceptible and resistant alleles. Plos Pathog., 8:e1002958-e1002958, 2012 Cited by PubMed 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, TEP1*S and TEP1*R, 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 TEP1*S1 allele which, while similar to the previously determined structure of full-length TEP1*R1, displays flexibility in the N-terminal fragment comprising domains MG1-MG6. Amino acid differences between TEP1*R1 and TEP1*S1 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 TEP1*S1 (TEP1*S1(cut)) is significantly more susceptible to hydrolysis of its intramolecular thioester bond than TEP1*R1(cut). TEP1*S1(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. PubMed: 23055931DOI: 10.1371/journal.ppat.1002958 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.7 Å) |
Structure validation
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