View source for 7lkb


==Crystal structure of PfCSP peptide 21 with vaccine-elicited human anti-malaria antibody m42.127==
<StructureSection load='7lkb' size='340' side='right'caption='[[7lkb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lkb]] 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_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKB 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7lkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lkb OCA], [https://pdbe.org/7lkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lkb RCSB], [https://www.ebi.ac.uk/pdbsum/7lkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lkb 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]
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== Publication Abstract from PubMed ==
Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity. One such antibody, iGL-CIS43.D3, was significantly more potent than the current best-in-class PfCSP-directed antibody. We found that vaccination with a junctional epitope peptide was more effective than full-length PfCSP at recruiting iGL-CIS43 B cells to germinal centers. Structure-function analysis revealed multiple somatic hypermutations that combinatorically improved protection. This mouse model can thus be used to understand vaccine immunogens and to develop highly potent anti-malarial antibodies.

Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies.,Kratochvil S, Shen CH, Lin YC, Xu K, Nair U, Da Silva Pereira L, Tripathi P, Arnold J, Chuang GY, Melzi E, Schon A, Zhang B, Dillon M, Bonilla B, Flynn BJ, Kirsch KH, Kisalu NK, Kiyuka PK, Liu T, Ou L, Pancera M, Rawi R, Reveiz M, Seignon K, Wang LT, Waring MT, Warner J, Yang Y, Francica JR, Idris AH, Seder RA, Kwong PD, Batista FD Immunity. 2021 Dec 14;54(12):2859-2876.e7. doi: 10.1016/j.immuni.2021.10.017. , Epub 2021 Nov 16. PMID:34788599<ref>PMID:34788599</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lkb" 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 3D7]]
[[Category: Kwong PD]]
[[Category: Xu K]]