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4LNV

Crystal Structure of TEP1s

Replaces:  4D93
Summary for 4LNV
Entry DOI10.2210/pdb4lnv/pdb
Related4D94
DescriptorThioester-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 Keywordsimmune system, innate immunity, lrim1 and apl1c
Biological sourceAnopheles gambiae (African malaria mosquito)
Total number of polymer chains3
Total formula weight455823.30
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 citationLe, 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: 23055931
DOI: 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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