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| <StructureSection load='3vdj' size='340' side='right'caption='[[3vdj]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='3vdj' size='340' side='right'caption='[[3vdj]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3vdj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vdj]] is a 1 chain structure with sequence from [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=3VDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VDJ FirstGlance]. <br> |
- | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vdk|3vdk]], [[3vdl|3vdl]]</div></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]] 1.698Å</td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFC0210c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
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| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vdj OCA], [https://pdbe.org/3vdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vdj RCSB], [https://www.ebi.ac.uk/pdbsum/3vdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vdj ProSAT]</span></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=3vdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vdj OCA], [https://pdbe.org/3vdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vdj RCSB], [https://www.ebi.ac.uk/pdbsum/3vdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vdj ProSAT]</span></td></tr> |
| </table> | | </table> |
- | <div style="background-color:#fffaf0;">
| + | == Function == |
- | == Publication Abstract from PubMed == | + | [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] |
- | Circumsporozoite (CS) protein is the major surface component of Plasmodium falciparum sporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an "alphaTSR" domain. The alphaTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but alphaTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized alphaTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.
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- | | + | |
- | Unexpected fold in the circumsporozoite protein target of malaria vaccines.,Doud MB, Koksal AC, Mi LZ, Song G, Lu C, Springer TA Proc Natl Acad Sci U S A. 2012 Apr 30. PMID:22547819<ref>PMID:22547819</ref>
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- | | + | |
- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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- | </div>
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- | <div class="pdbe-citations 3vdj" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Plaf7]] | + | [[Category: Plasmodium falciparum 3D7]] |
- | [[Category: Doud, M B]] | + | [[Category: Doud MB]] |
- | [[Category: Koksal, A C]] | + | [[Category: Koksal AC]] |
- | [[Category: Lu, C]] | + | [[Category: Lu C]] |
- | [[Category: Mi, L Z]] | + | [[Category: Mi LZ]] |
- | [[Category: Song, G]] | + | [[Category: Song G]] |
- | [[Category: Springer, T A]] | + | [[Category: Springer TA]] |
- | [[Category: Atsr]]
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- | [[Category: Cell invasion]]
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- | [[Category: Tsr]]
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| Structural highlights
Function
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][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]
References
- ↑ Tan J, Sack BK, Oyen D, Zenklusen I, Piccoli L, Barbieri S, Foglierini M, Fregni CS, Marcandalli J, Jongo S, Abdulla S, Perez L, Corradin G, Varani L, Sallusto F, Sim BKL, Hoffman SL, Kappe SHI, Daubenberger C, Wilson IA, Lanzavecchia A. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med. 2018 Mar 19. pii: nm.4513. doi: 10.1038/nm.4513. PMID:29554084 doi:http://dx.doi.org/10.1038/nm.4513
- ↑ Oyen D, Torres JL, Aoto PC, Flores-Garcia Y, Binter S, Pholcharee T, Carroll S, Reponen S, Wash R, Liang Q, Lemiale F, Locke E, Bradley A, King CR, Emerling D, Kellam P, Zavala F, Ward AB, Wilson IA. Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein. PLoS Pathog. 2020 Mar 9;16(3):e1008373. doi: 10.1371/journal.ppat.1008373. PMID:32150583 doi:http://dx.doi.org/10.1371/journal.ppat.1008373
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