4lnv | pdb_00004lnv
Crystal Structure of TEP1s
Structural highlights
FunctionTEPS1_ANOGA Plays an essential role in the innate immune response to bacteria and protozoa infection (PubMed:11257225). After proteolytic cleavage, the protein C-terminus binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance either by melanization or lysis (PubMed:11257225). Initiate the recruitment and activation of a cascade of proteases, mostly of CLIP-domain serine proteases, which leads to the proteolytic cleavage of the prophenoloxidase (PPO) into active phenoloxidase (PO), the rate-limiting enzyme in melanin biosynthesis (By similarity). In response to parasite P.berghei-mediated infection, binds to and mediates killing of ookinetes, as they egress from midgut epithelial cells into the basal labyrinth, by both lysis and melanization (By similarity). During bacterial infection, binds to both Gram-positive and Gram-negative bacteria but only promotes phagocytosis of Gram-negative bacteria (PubMed:11257225). Promotes the accumulation of SPCLIP1 onto the surface of P.berghei ookinetes and bacterium E.coli which leads to the melanization of the pathogen (By similarity). Recruits CLIPA2 to bacteria surface (By similarity). In response to bacterial infection, required for periostial hemocyte aggregation, but not for the aggregation of sessile hemocytes in non-periostial regions (By similarity). During the late stage of fungus B.bassiana-mediated infection, required for the initiation of hyphae melanization by binding to the surface of hyphae and recruiting prophenoloxidase PPO to them (By similarity). Plays a role in male fertility by binding to defective sperm cells and promoting their removal during spermatogenesis (PubMed:26394016).[UniProtKB:C9XI63][1] [2] Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance.[3] Publication Abstract from PubMedThioester-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. Molecular Basis for Genetic Resistance of Anopheles gambiae to Plasmodium: Structural Analysis of TEP1 Susceptible and Resistant Alleles.,Le BV, Williams M, Logarajah S, Baxter RH PLoS Pathog. 2012 Oct;8(10):e1002958. doi: 10.1371/journal.ppat.1002958. Epub, 2012 Oct 4. PMID:23055931[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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