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| | ==Crystal structure of AED7-norepineprhine complex== | | ==Crystal structure of AED7-norepineprhine complex== |
| - | <StructureSection load='3dye' size='340' side='right' caption='[[3dye]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='3dye' size='340' side='right'caption='[[3dye]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dye]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aedes_aegypti Aedes aegypti]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DYE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DYE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dye]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aedes_aegypti Aedes aegypti]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DYE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LNR:L-NOREPINEPHRINE'>LNR</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]] 1.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dy9|3dy9]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LNR:L-NOREPINEPHRINE'>LNR</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">D7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7159 Aedes aegypti])</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=3dye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dye OCA], [https://pdbe.org/3dye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dye RCSB], [https://www.ebi.ac.uk/pdbsum/3dye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dye 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=3dye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dye OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dye RCSB], [http://www.ebi.ac.uk/pdbsum/3dye PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/D7L1_AEDAE D7L1_AEDAE] Modulates blood feeding of female mosquitoes on vertebrate species by binding and sequestering different mediators involved in the host response, such as biogenic amines and eicosanoids (PubMed:32799410, PubMed:37909749). Binds serotonin, histamine, leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4, adrenaline and noradrenaline (PubMed:16301315, PubMed:19234127, PubMed:32799410). Does not bind tryptamine and U-46619, a stable analog of thromboxane A2 (PubMed:19234127, PubMed:32799410). Exhibits vasodilating activity (PubMed:32799410). Inhibits agonist-induced platelet aggregation but not blood clotting (PubMed:32799410). Inhibits noradrenaline-induced smooth muscle contraction (PubMed:16301315). Promotes an influx of host neutrophils at the inoculation site (PubMed:38378891).<ref>PMID:16301315</ref> <ref>PMID:19234127</ref> <ref>PMID:32799410</ref> <ref>PMID:37909749</ref> <ref>PMID:38378891</ref> (Microbial infection) Probably promotes Plasmodium gallinaceum oocyst development in mosquito midgut.<ref>PMID:37909749</ref> (Microbial infection) Exhibits antiviral activity against dengue virus type 2 probably through a direct interaction with dengue virus virions.<ref>PMID:27632170</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dy/3dye_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dy/3dye_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> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3dye ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3dye" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Aedes aegypti]] | | [[Category: Aedes aegypti]] |
| - | [[Category: Andersen, J F]] | + | [[Category: Large Structures]] |
| - | [[Category: Calvo, E]] | + | [[Category: Andersen JF]] |
| - | [[Category: Mans, B J]] | + | [[Category: Calvo E]] |
| - | [[Category: Ribeiro, J M]] | + | [[Category: Mans BJ]] |
| - | [[Category: All-helical]] | + | [[Category: Ribeiro JM]] |
| - | [[Category: Allergen]]
| + | |
| - | [[Category: Odorant-binding protein]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
Function
D7L1_AEDAE Modulates blood feeding of female mosquitoes on vertebrate species by binding and sequestering different mediators involved in the host response, such as biogenic amines and eicosanoids (PubMed:32799410, PubMed:37909749). Binds serotonin, histamine, leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4, adrenaline and noradrenaline (PubMed:16301315, PubMed:19234127, PubMed:32799410). Does not bind tryptamine and U-46619, a stable analog of thromboxane A2 (PubMed:19234127, PubMed:32799410). Exhibits vasodilating activity (PubMed:32799410). Inhibits agonist-induced platelet aggregation but not blood clotting (PubMed:32799410). Inhibits noradrenaline-induced smooth muscle contraction (PubMed:16301315). Promotes an influx of host neutrophils at the inoculation site (PubMed:38378891).[1] [2] [3] [4] [5] (Microbial infection) Probably promotes Plasmodium gallinaceum oocyst development in mosquito midgut.[6] (Microbial infection) Exhibits antiviral activity against dengue virus type 2 probably through a direct interaction with dengue virus virions.[7]
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
The mosquito D7 salivary proteins are encoded by a multigene family related to the arthropod odorant-binding protein (OBP) superfamily. Forms having either one or two OBP domains are found in mosquito saliva. Four single-domain and one two-domain D7 proteins from Anopheles gambiae and Aedes aegypti (AeD7), respectively, were shown to bind biogenic amines with high affinity and with a stoichiometry of one ligand per protein molecule. Sequence comparisons indicated that only the C-terminal domain of AeD7 is homologous to the single-domain proteins from A. gambiae, suggesting that the N-terminal domain may bind a different class of ligands. Here, we describe the 3D structure of AeD7 and examine the ligand-binding characteristics of the N- and C-terminal domains. Isothermal titration calorimetry and ligand complex crystal structures show that the N-terminal domain binds cysteinyl leukotrienes (cysLTs) with high affinities (50-60 nM) whereas the C-terminal domain binds biogenic amines. The lipid chain of the cysLT binds in a hydrophobic pocket of the N-terminal domain, whereas binding of norepinephrine leads to an ordering of the C-terminal portion of the C-terminal domain into an alpha-helix that, along with rotations of Arg-176 and Glu-268 side chains, acts to bury the bound ligand.
Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein.,Calvo E, Mans BJ, Ribeiro JM, Andersen JF Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3728-33. Epub 2009 Feb 20. PMID:19234127[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Calvo E, Mans BJ, Andersen JF, Ribeiro JM. Function and evolution of a mosquito salivary protein family. J Biol Chem. 2006 Jan 27;281(4):1935-42. PMID:16301315 doi:10.1074/jbc.M510359200
- ↑ Calvo E, Mans BJ, Ribeiro JM, Andersen JF. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3728-33. Epub 2009 Feb 20. PMID:19234127
- ↑ Martin-Martin I, Kern O, Brooks S, Smith LB, Valenzuela-Leon PC, Bonilla B, Ackerman H, Calvo E. Biochemical characterization of AeD7L2 and its physiological relevance in blood feeding in the dengue mosquito vector, Aedes aegypti. FEBS J. 2021 Mar;288(6):2014-2029. PMID:32799410 doi:10.1111/febs.15524
- ↑ Martin-Martin I, Kojin BB, Aryan A, Williams AE, Molina-Cruz A, Valenzuela-Leon PC, Shrivastava G, Botello K, Minai M, Adelman ZN, Calvo E. Aedes aegypti D7 long salivary proteins modulate blood feeding and parasite infection. mBio. 2023 Dec 19;14(6):e0228923. PMID:37909749 doi:10.1128/mbio.02289-23
- ↑ Wang Z, Nie K, Liang Y, Niu J, Yu X, Zhang O, Liu L, Shi X, Wang Y, Feng X, Zhu Y, Wang P, Cheng G. A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission. EMBO J. 2024 May;43(9):1690-1721. PMID:38378891 doi:10.1038/s44318-024-00056-x
- ↑ Martin-Martin I, Kojin BB, Aryan A, Williams AE, Molina-Cruz A, Valenzuela-Leon PC, Shrivastava G, Botello K, Minai M, Adelman ZN, Calvo E. Aedes aegypti D7 long salivary proteins modulate blood feeding and parasite infection. mBio. 2023 Dec 19;14(6):e0228923. PMID:37909749 doi:10.1128/mbio.02289-23
- ↑ Conway MJ, Londono-Renteria B, Troupin A, Watson AM, Klimstra WB, Fikrig E, Colpitts TM. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection. PLoS Negl Trop Dis. 2016 Sep 15;10(9):e0004941. PMID:27632170 doi:10.1371/journal.pntd.0004941
- ↑ Calvo E, Mans BJ, Ribeiro JM, Andersen JF. Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3728-33. Epub 2009 Feb 20. PMID:19234127
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