4D94

Crystal Structure of TEP1r

4D94 の概要

• エントリーDOI: 10.2210/pdb4d94/pdb
• 関連するPDBエントリー: 4D93
• 分子名称: Thioester-containing protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: plasmodium refractory allele, immune system, full-length protein, thioester, macroglobulin domains, component of innate immune response by the opsinization and melanization of pathogens
• 由来する生物種: Anopheles gambiae (African malaria mosquito)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 151967.18

構造登録者

Le, B.V.,Williams, M.,Logarajah, S.,Baxter, R.H.G. (登録日: 2012-01-11, 公開日: 2012-10-17, 最終更新日: 2024-10-16)

主引用文献

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

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

実験手法

X-RAY DIFFRACTION (2.7 Å)