7rxp: Difference between revisions
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==== | ==Fab1512 in complex with the C-terminal alpha-TSR domain of P. falciparum== | ||
<StructureSection load='7rxp' size='340' side='right'caption='[[7rxp]]' scene=''> | <StructureSection load='7rxp' size='340' side='right'caption='[[7rxp]], [[Resolution|resolution]] 1.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rxp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RXP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RXP FirstGlance]. <br> | ||
</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=7rxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rxp OCA], [https://pdbe.org/7rxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rxp RCSB], [https://www.ebi.ac.uk/pdbsum/7rxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rxp ProSAT]</span></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]] 1.761Å</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=7rxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rxp OCA], [https://pdbe.org/7rxp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rxp RCSB], [https://www.ebi.ac.uk/pdbsum/7rxp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rxp ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CSP_PLAF7 CSP_PLAF7] Essential sporozoite protein (PubMed:29554084, PubMed:32150583). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (By similarity). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:29554084, PubMed:32150583). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity).[UniProtKB:P23093]<ref>PMID:29554084</ref> <ref>PMID:32150583</ref> In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[UniProtKB:P23093] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted alpha-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved beta-sheet face of the ctCSP (denoted beta-ctCSP). Antibodies to the beta-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the alpha-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the beta-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design. | |||
A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.,Beutler N, Pholcharee T, Oyen D, Flores-Garcia Y, MacGill RS, Garcia E, Calla J, Parren M, Yang L, Volkmuth W, Locke E, Regules JA, Dutta S, Emerling D, Early AM, Neafsey DE, Winzeler EA, King CR, Zavala F, Burton DR, Wilson IA, Rogers TF PLoS Pathog. 2022 Mar 28;18(3):e1010409. doi: 10.1371/journal.ppat.1010409. , eCollection 2022 Mar. PMID:35344575<ref>PMID:35344575</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rxp" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Plasmodium falciparum 3D7]] | ||
[[Category: Oyen D]] | |||
[[Category: Pholcharee T]] | |||
[[Category: Wilson IA]] | |||
Latest revision as of 14:38, 30 October 2024
Fab1512 in complex with the C-terminal alpha-TSR domain of P. falciparumFab1512 in complex with the C-terminal alpha-TSR domain of P. falciparum
Structural highlights
FunctionCSP_PLAF7 Essential sporozoite protein (PubMed:29554084, PubMed:32150583). In the mosquito vector, required for sporozoite development in the oocyst, migration through the vector hemolymph and entry into the vector salivary glands (By similarity). In the vertebrate host, required for sporozoite migration through the host dermis and infection of host hepatocytes (PubMed:29554084, PubMed:32150583). Binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes (By similarity).[UniProtKB:P23093][1] [2] In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.[UniProtKB:P23093] Publication Abstract from PubMedPotent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted alpha-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved beta-sheet face of the ctCSP (denoted beta-ctCSP). Antibodies to the beta-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the alpha-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the beta-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design. A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.,Beutler N, Pholcharee T, Oyen D, Flores-Garcia Y, MacGill RS, Garcia E, Calla J, Parren M, Yang L, Volkmuth W, Locke E, Regules JA, Dutta S, Emerling D, Early AM, Neafsey DE, Winzeler EA, King CR, Zavala F, Burton DR, Wilson IA, Rogers TF PLoS Pathog. 2022 Mar 28;18(3):e1010409. doi: 10.1371/journal.ppat.1010409. , eCollection 2022 Mar. PMID:35344575[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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