6d0x: Difference between revisions
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The | ==Crystal structure of chimeric H.2140 / K.1210 Fab in complex with circumsporozoite protein NANP3== | ||
<StructureSection load='6d0x' size='340' side='right'caption='[[6d0x]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6d0x]] is a 3 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=6D0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D0X 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]] 1.849Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=6d0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d0x OCA], [https://pdbe.org/6d0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d0x RCSB], [https://www.ebi.ac.uk/pdbsum/6d0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d0x 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 == | |||
Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens. | |||
Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.,Imkeller K, Scally SW, Bosch A, Marti GP, Costa G, Triller G, Murugan R, Renna V, Jumaa H, Kremsner PG, Sim BKL, Hoffman SL, Mordmuller B, Levashina E, Julien JP, Wardemann H Science. 2018 Jun 7. pii: science.aar5304. doi: 10.1126/science.aar5304. PMID:29880723<ref>PMID:29880723</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6d0x" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum]] | |||
[[Category: Bosch A]] | |||
[[Category: Imkeller K]] | |||
[[Category: Julien JP]] | |||
[[Category: Scally SW]] | |||
[[Category: Wardemann H]] | |||
Latest revision as of 11:58, 9 October 2024
Crystal structure of chimeric H.2140 / K.1210 Fab in complex with circumsporozoite protein NANP3Crystal structure of chimeric H.2140 / K.1210 Fab in complex with circumsporozoite protein NANP3
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 PubMedAffinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens. Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.,Imkeller K, Scally SW, Bosch A, Marti GP, Costa G, Triller G, Murugan R, Renna V, Jumaa H, Kremsner PG, Sim BKL, Hoffman SL, Mordmuller B, Levashina E, Julien JP, Wardemann H Science. 2018 Jun 7. pii: science.aar5304. doi: 10.1126/science.aar5304. PMID:29880723[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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