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==Crystal structure of 4498 Fab in complex with circumsporozoite protein NDN3 and anti-Kappa VHH domain== | ==Crystal structure of 4498 Fab in complex with circumsporozoite protein NDN3 and anti-Kappa VHH domain== | ||
<StructureSection load='6ulf' size='340' side='right'caption='[[6ulf]]' scene=''> | <StructureSection load='6ulf' size='340' side='right'caption='[[6ulf]], [[Resolution|resolution]] 1.70Å' 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=6ULF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ULF FirstGlance]. <br> | <table><tr><td colspan='2'>[[6ulf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ULF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ULF FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ulf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ulf OCA], [http://pdbe.org/6ulf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ulf RCSB], [http://www.ebi.ac.uk/pdbsum/6ulf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ulf ProSAT]</span></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ulf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ulf OCA], [http://pdbe.org/6ulf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ulf RCSB], [http://www.ebi.ac.uk/pdbsum/6ulf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ulf ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/CSP_PLAFA CSP_PLAFA]] The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses. | |||
Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs.,Murugan R, Scally SW, Costa G, Mustafa G, Thai E, Decker T, Bosch A, Prieto K, Levashina EA, Julien JP, Wardemann H Nat Med. 2020 May 25. pii: 10.1038/s41591-020-0881-9. doi:, 10.1038/s41591-020-0881-9. PMID:32451496<ref>PMID:32451496</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6ulf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Julien | [[Category: Julien, J P]] | ||
[[Category: Murugan R]] | [[Category: Murugan, R]] | ||
[[Category: Prieto K]] | [[Category: Prieto, K]] | ||
[[Category: Scally | [[Category: Scally, S W]] | ||
[[Category: Thai E]] | [[Category: Thai, E]] | ||
[[Category: Wardemann H]] | [[Category: Wardemann, H]] | ||
[[Category: Antibody]] | |||
[[Category: Immune system]] | |||
[[Category: Malaria]] | |||
Revision as of 10:04, 25 June 2020
Crystal structure of 4498 Fab in complex with circumsporozoite protein NDN3 and anti-Kappa VHH domainCrystal structure of 4498 Fab in complex with circumsporozoite protein NDN3 and anti-Kappa VHH domain
Structural highlights
Function[CSP_PLAFA] The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). Publication Abstract from PubMedThe circumsporozoite protein of the human malaria parasite Plasmodium falciparum (PfCSP) is the main target of antibodies that prevent the infection and disease, as shown in animal models. However, the limited efficacy of the PfCSP-based vaccine RTS,S calls for a better understanding of the mechanisms driving the development of the most potent human PfCSP antibodies and identification of their target epitopes. By characterizing 200 human monoclonal PfCSP antibodies induced by sporozoite immunization, we establish that the most potent antibodies bind around a conserved (N/D)PNANPN(V/A) core. High antibody affinity to the core correlates with protection from parasitemia in mice and evolves around the recognition of NANP motifs. The data suggest that the rational design of a next-generation PfCSP vaccine that elicits high-affinity antibody responses against the core epitope will promote the induction of protective humoral immune responses. Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs.,Murugan R, Scally SW, Costa G, Mustafa G, Thai E, Decker T, Bosch A, Prieto K, Levashina EA, Julien JP, Wardemann H Nat Med. 2020 May 25. pii: 10.1038/s41591-020-0881-9. doi:, 10.1038/s41591-020-0881-9. PMID:32451496[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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