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| | ==Crystal Structure of TEP1s== | | ==Crystal Structure of TEP1s== |
| - | <StructureSection load='4lnv' size='340' side='right' caption='[[4lnv]], [[Resolution|resolution]] 3.70Å' scene=''> | + | <StructureSection load='4lnv' size='340' side='right'caption='[[4lnv]], [[Resolution|resolution]] 3.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lnv]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Anoga Anoga]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4d93 4d93]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LNV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LNV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lnv]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4d93 4d93]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LNV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 3.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4d94|4d94]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TEP-I, tep1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7165 ANOGA])</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=4lnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lnv OCA], [https://pdbe.org/4lnv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lnv RCSB], [https://www.ebi.ac.uk/pdbsum/4lnv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lnv ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lnv OCA], [http://pdbe.org/4lnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lnv RCSB], [http://www.ebi.ac.uk/pdbsum/4lnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lnv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/TEPS1_ANOGA TEPS1_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]<ref>PMID:11257225</ref> <ref>PMID:26394016</ref> Binds covalently through a thioester bond to the pathogen surface resulting in pathogen clearance.<ref>PMID:11257225</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Anoga]] | + | [[Category: Anopheles gambiae]] |
| - | [[Category: Baxter, R H.G]] | + | [[Category: Large Structures]] |
| - | [[Category: Le, B V]] | + | [[Category: Baxter RHG]] |
| - | [[Category: Logarajah, S]] | + | [[Category: Le BV]] |
| - | [[Category: Williams, M]] | + | [[Category: Logarajah S]] |
| - | [[Category: Immune system]] | + | [[Category: Williams M]] |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Lrim1 and apl1c]]
| + | |
| Structural highlights
Function
TEPS1_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 PubMed
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.
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
- ↑ Levashina EA, Moita LF, Blandin S, Vriend G, Lagueux M, Kafatos FC. Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell. 2001 Mar 9;104(5):709-18. doi: 10.1016/s0092-8674(01)00267-7. PMID:11257225 doi:http://dx.doi.org/10.1016/s0092-8674(01)00267-7
- ↑ 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
- ↑ Levashina EA, Moita LF, Blandin S, Vriend G, Lagueux M, Kafatos FC. Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell. 2001 Mar 9;104(5):709-18. doi: 10.1016/s0092-8674(01)00267-7. PMID:11257225 doi:http://dx.doi.org/10.1016/s0092-8674(01)00267-7
- ↑ Le BV, Williams M, Logarajah S, Baxter RH. Molecular Basis for Genetic Resistance of Anopheles gambiae to Plasmodium: Structural Analysis of TEP1 Susceptible and Resistant Alleles. PLoS Pathog. 2012 Oct;8(10):e1002958. doi: 10.1371/journal.ppat.1002958. Epub, 2012 Oct 4. PMID:23055931 doi:10.1371/journal.ppat.1002958
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