6wg2: Difference between revisions
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The | ==Crystal structure of Fab239 in complex with NPNA4 peptide from circumsporozoite protein== | ||
<StructureSection load='6wg2' size='340' side='right'caption='[[6wg2]], [[Resolution|resolution]] 2.53Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6wg2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WG2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.534Å</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=6wg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wg2 OCA], [https://pdbe.org/6wg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wg2 RCSB], [https://www.ebi.ac.uk/pdbsum/6wg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wg2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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 most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I beta- and Asn pseudo 3(10) turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization. | |||
Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum.,Pholcharee T, Oyen D, Flores-Garcia Y, Gonzalez-Paez G, Han Z, Williams KL, Volkmuth W, Emerling D, Locke E, Richter King C, Zavala F, Wilson IA Nat Commun. 2021 Feb 16;12(1):1063. doi: 10.1038/s41467-021-21221-4. PMID:33594061<ref>PMID:33594061</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6wg2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum]] | |||
[[Category: Oyen D]] | |||
[[Category: Pholcharee T]] | |||
[[Category: Wilson IA]] | |||
Latest revision as of 13:38, 23 October 2024
Crystal structure of Fab239 in complex with NPNA4 peptide from circumsporozoite proteinCrystal structure of Fab239 in complex with NPNA4 peptide from circumsporozoite protein
Structural highlights
FunctionCSP_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 most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable antibody responses. Here, we elucidate crystal structures, binding affinities and kinetics, and in vivo protection of eight anti-NANP antibodies derived from an RTS,S phase 2a trial and encoded by three different heavy-chain germline genes. The structures reinforce the importance of homotypic Fab-Fab interactions in protective antibodies and the overwhelmingly dominant preference for a germline-encoded aromatic residue for recognition of the NANP motif. In this study, antibody apparent affinity correlates best with protection in an in vivo mouse model, with the more potent antibodies also recognizing epitopes with repeating secondary structural motifs of type I beta- and Asn pseudo 3(10) turns; such insights can be incorporated into design of more effective immunogens and antibodies for passive immunization. Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum.,Pholcharee T, Oyen D, Flores-Garcia Y, Gonzalez-Paez G, Han Z, Williams KL, Volkmuth W, Emerling D, Locke E, Richter King C, Zavala F, Wilson IA Nat Commun. 2021 Feb 16;12(1):1063. doi: 10.1038/s41467-021-21221-4. PMID:33594061[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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