|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2pn5' size='340' side='right'caption='[[2pn5]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='2pn5' size='340' side='right'caption='[[2pn5]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pn5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anoga Anoga]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PN5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pn5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PN5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PN5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.698Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEP-I ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7165 ANOGA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pn5 OCA], [https://pdbe.org/2pn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pn5 RCSB], [https://www.ebi.ac.uk/pdbsum/2pn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pn5 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pn5 OCA], [https://pdbe.org/2pn5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pn5 RCSB], [https://www.ebi.ac.uk/pdbsum/2pn5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pn5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TEPR1_ANOGA TEPR1_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]<ref>PMID:15006349</ref> <ref>PMID:19286136</ref> <ref>PMID:26394016</ref> Binds to and mediates killing of parasite P.bergei ookinetes by lysis and melanization.<ref>PMID:15006349</ref> Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance.[UniProtKB:Q9GYW4] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 13: |
Line 15: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pn5_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pn5_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 31: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Anoga]] | + | [[Category: Anopheles gambiae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baxter, R H.G]] | + | [[Category: Baxter RHG]] |
| - | [[Category: Full-length mature peptide]]
| + | |
| - | [[Category: Immune system]]
| + | |
| Structural highlights
Function
TEPR1_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 PubMed
Thioester-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
- ↑ Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA. Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell. 2004 Mar 5;116(5):661-70. doi: 10.1016/s0092-8674(04)00173-4. PMID:15006349 doi:http://dx.doi.org/10.1016/s0092-8674(04)00173-4
- ↑ Fraiture M, Baxter RH, Steinert S, Chelliah Y, Frolet C, Quispe-Tintaya W, Hoffmann JA, Blandin SA, Levashina EA. Two mosquito LRR proteins function as complement control factors in the TEP1-mediated killing of Plasmodium. Cell Host Microbe. 2009 Mar 19;5(3):273-84. doi: 10.1016/j.chom.2009.01.005. PMID:19286136 doi:http://dx.doi.org/10.1016/j.chom.2009.01.005
- ↑ Pompon J, Levashina EA. A New Role of the Mosquito Complement-like Cascade in Male Fertility in Anopheles gambiae. PLoS Biol. 2015 Sep 22;13(9):e1002255. doi: 10.1371/journal.pbio.1002255., eCollection 2015. PMID:26394016 doi:http://dx.doi.org/10.1371/journal.pbio.1002255
- ↑ Blandin S, Shiao SH, Moita LF, Janse CJ, Waters AP, Kafatos FC, Levashina EA. Complement-like protein TEP1 is a determinant of vectorial capacity in the malaria vector Anopheles gambiae. Cell. 2004 Mar 5;116(5):661-70. doi: 10.1016/s0092-8674(04)00173-4. PMID:15006349 doi:http://dx.doi.org/10.1016/s0092-8674(04)00173-4
- ↑ Baxter RH, Chang CI, Chelliah Y, Blandin S, Levashina EA, Deisenhofer J. Structural basis for conserved complement factor-like function in the antimalarial protein TEP1. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11615-20. Epub 2007 Jul 2. PMID:17606907
|
