8fg0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the 3764 Fab in complex with the C-terminal PfCSP linker, PfCSP281-294.== | |
| + | <StructureSection load='8fg0' size='340' side='right'caption='[[8fg0]], [[Resolution|resolution]] 2.36Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8fg0]] is a 6 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=8FG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FG0 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]] 2.36Å</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=8fg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fg0 OCA], [https://pdbe.org/8fg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fg0 RCSB], [https://www.ebi.ac.uk/pdbsum/8fg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fg0 ProSAT]</span></td></tr> | ||
| + | </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 == | ||
| + | Human monoclonal antibodies (mAbs) against the central repeat and junction domain of Plasmodium falciparum circumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the alpha-thrombospondin repeat (alpha-TSR) domain. Specificity for the polymorphic Th2R/Th3R but not the conserved RII+/CS.T3 region in the alpha-TSR was associated with IGHV3-21/IGVL3-21 or IGLV3-1 gene usage. Although the C terminus specific mAbs showed signs of more efficient affinity maturation and class-switching compared to anti-repeat mAbs, live sporozoite binding and inhibitory activity was limited to a single C-linker reactive mAb with cross-reactivity to the central repeat and junction. The data provide novel insights in the human anti-C-linker and anti-alpha-TSR antibody response that support exclusion of the PfCSP C terminus from malaria vaccine designs. | ||
| - | + | Molecular and functional properties of human Plasmodium falciparum CSP C-terminus antibodies.,Oludada OE, Costa G, Burn Aschner C, Obraztsova AS, Prieto K, Canetta C, Hoffman SL, Kremsner PG, Mordmuller B, Murugan R, Julien JP, Levashina EA, Wardemann H EMBO Mol Med. 2023 Jun 7;15(6):e17454. doi: 10.15252/emmm.202317454. Epub 2023 , Apr 21. PMID:37082831<ref>PMID:37082831</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8fg0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Plasmodium falciparum]] | ||
| + | [[Category: Burn Aschner C]] | ||
| + | [[Category: Julien JP]] | ||
Current revision
Crystal structure of the 3764 Fab in complex with the C-terminal PfCSP linker, PfCSP281-294.
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