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| | ==Protective cellular immunity against P. falciparum malaria merozoite is associated with a different P7 and P8 residue orientation in the MHC-peptide-TCR complex== | | ==Protective cellular immunity against P. falciparum malaria merozoite is associated with a different P7 and P8 residue orientation in the MHC-peptide-TCR complex== |
| - | <StructureSection load='2mug' size='340' side='right' caption='[[2mug]], [[NMR_Ensembles_of_Models | 22 NMR models]]' scene=''> | + | <StructureSection load='2mug' size='340' side='right'caption='[[2mug]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mug]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MUG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mug]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_FCR-3/Gambia Plasmodium falciparum FCR-3/Gambia]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MUG FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 22 models</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=2mug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mug OCA], [http://pdbe.org/2mug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mug RCSB], [http://www.ebi.ac.uk/pdbsum/2mug PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2mug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mug OCA], [https://pdbe.org/2mug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mug RCSB], [https://www.ebi.ac.uk/pdbsum/2mug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mug ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SERA_PLAFG SERA_PLAFG]] It may function at the red blood cell membrane, perhaps as a component that influences the invasion process. | + | [https://www.uniprot.org/uniprot/SERA5_PLAFG SERA5_PLAFG] Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (By similarity). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (By similarity).[UniProtKB:Q9TY95] May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (PubMed:12244052).[UniProtKB:P69193]<ref>PMID:12244052</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: Cifuentes, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Delgado, G]] | + | [[Category: Plasmodium falciparum FCR-3/Gambia]] |
| - | [[Category: Lozano, J]] | + | [[Category: Cifuentes G]] |
| - | [[Category: Patarroyo, M]] | + | [[Category: Delgado G]] |
| - | [[Category: Rivera, Z]] | + | [[Category: Lozano J]] |
| - | [[Category: Rosas, J]] | + | [[Category: Patarroyo M]] |
| - | [[Category: Salazar, L]] | + | [[Category: Rivera Z]] |
| - | [[Category: Vargas, L]] | + | [[Category: Rosas J]] |
| - | [[Category: Peptide binding protein]]
| + | [[Category: Salazar L]] |
| | + | [[Category: Vargas L]] |
| Structural highlights
Function
SERA5_PLAFG Plays an essential role during the asexual blood stage development by controlling the kinetics of merozoite egress from host erythrocytes (By similarity). Specifically, prevents premature rupture of the parasitophorous vacuole and host erythrocyte membranes (By similarity).[UniProtKB:Q9TY95] May prevent merozoite phagocytosis by host monocytes via interaction with host VTN at the merozoite surface (By similarity). Plays a role in parasite growth (PubMed:12244052).[UniProtKB:P69193][1]
Publication Abstract from PubMed
Developing a logical and rational methodology for obtaining vaccines, especially against the main parasite causing human malaria (P. falciparum), consists of blocking receptor-ligand interactions. Conserved peptides derived from proteins involved in invasion and having high red blood cell binding ability have thus been identified. Immunization studies using Aotus monkeys have revealed that these peptides were neither immunogenic nor protection inducing. When modified in their critical binding residues, previously identified by Glycine scanning, some of these peptides were immunogenic and non-protection inducers; others induced short-lived antibodies whilst a few were both immunogenic and protection inducing. However, very few of these modified high activity binding peptides (HABPs) reproducibly induced protection without inducing antibody production, but with high cytokine liberation, suggesting that cellular mechanisms had been activated in the protection process. The three-dimensional structure of these peptides inducing protection without producing antibodies was determined by 1H-NMR. Their HLA-DRbeta1* molecule binding ability was also determined to ascertain association between their 3D structure and ability to bind to Major Histocompatibility Complex Class-II molecules (MHC-II). 1H Nuclear Magnetic Resonance analysis and structure calculations clearly showed that these modified HABPs inducing protective cellular immune responses (but not producing antibodies against malaria) adopted special structural configuration to fit into the MHC II-peptide-TCR complex. A different orientation for P7 and P8 TCR contacting residues was clearly recognized when comparing their structure with modified peptides, which induced high antibody titers and protection, suggesting that these residues are involved in activating the immune system associated with antibody production and protection.
Protective cellular immunity against P. falciparum malaria merozoites is associated with a different P7 and P8 residue orientation in the MHC-peptide-TCR complex.,Patarroyo ME, Salazar LM, Cifuentes G, Lozano JM, Delgado G, Rivera Z, Rosas J, Vargas LE Biochimie. 2006 Feb;88(2):219-30. Epub 2005 Aug 18. PMID:16126320[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aoki S, Li J, Itagaki S, Okech BA, Egwang TG, Matsuoka H, Palacpac NM, Mitamura T, Horii T. Serine repeat antigen (SERA5) is predominantly expressed among the SERA multigene family of Plasmodium falciparum, and the acquired antibody titers correlate with serum inhibition of the parasite growth. J Biol Chem. 2002 Dec 6;277(49):47533-40. PMID:12244052 doi:10.1074/jbc.M207145200
- ↑ Patarroyo ME, Salazar LM, Cifuentes G, Lozano JM, Delgado G, Rivera Z, Rosas J, Vargas LE. Protective cellular immunity against P. falciparum malaria merozoites is associated with a different P7 and P8 residue orientation in the MHC-peptide-TCR complex. Biochimie. 2006 Feb;88(2):219-30. Epub 2005 Aug 18. PMID:16126320 doi:http://dx.doi.org/10.1016/j.biochi.2005.07.006
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