2pn5
From Proteopedia
Crystal Structure of TEP1r
Structural highlights
FunctionTEPR1_ANOGA Plays an essential role in the innate immune response against bacteria, fungi and protozoa infection (PubMed:15006349). 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:15006349, PubMed:19286136). 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 (PubMed:15006349, PubMed:19286136). During bacterial infection, binds to both Gram-positive and Gram-negative bacteria but only promotes phagocytosis of Gram-negative bacteria (By similarity). 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] [3] Binds to and mediates killing of parasite P.bergei ookinetes by lysis and melanization.[4] Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance.[UniProtKB:Q9GYW4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThioester-containing proteins (TEPs) are a major component of the innate immune response of insects to invasion by bacteria and protozoa. TEPs form a distinct clade of a superfamily that includes the pan-protease inhibitors alpha(2)-macroglobulins and vertebrate complement factors. The essential feature of these proteins is a sequestered thioester bond that, after cleavage in a protease-sensitive region of the protein, is activated and covalently binds to its target. Recently, TEP1 from the malarial vector Anopheles gambiae was shown to mediate recognition and killing of ookinetes from the malarial parasite Plasmodium berghei, a model for the human malarial parasite Plasmodium falciparum. Here, we present the crystal structure of the TEP1 isoform TEP1r. Although the overall protein fold of TEP1r resembles that of complement factor C3, the TEP1r domains are repositioned to stabilize the inactive conformation of the molecule (containing an intact thioester) in the absence of the anaphylotoxin domain, a central component of complement factors. The structure of TEP1r provides a molecular basis for the differences between TEP1 alleles TEP1r and TEP1s, which correlate with resistance of A. gambiae to infection by P. berghei. Structural basis for conserved complement factor-like function in the antimalarial protein TEP1.,Baxter RH, Chang CI, Chelliah Y, Blandin S, Levashina EA, Deisenhofer J Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11615-20. Epub 2007 Jul 2. PMID:17606907[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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