8dfg: Difference between revisions
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==Crystal structure of potently neutralizing human monoclonal antibody 42D6 Fab in complex with MSP1-19== | |||
<StructureSection load='8dfg' size='340' side='right'caption='[[8dfg]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8dfg]] 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=8DFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DFG 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]] 2Å</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=8dfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dfg OCA], [https://pdbe.org/8dfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dfg RCSB], [https://www.ebi.ac.uk/pdbsum/8dfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dfg ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Defining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions. | |||
Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion.,Patel PN, Dickey TH, Hopp CS, Diouf A, Tang WK, Long CA, Miura K, Crompton PD, Tolia NH Nat Commun. 2022 Oct 6;13(1):5888. doi: 10.1038/s41467-022-33336-3. PMID:36202833<ref>PMID:36202833</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8dfg" 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: Patel PN]] | |||
[[Category: Tang WK]] | |||
[[Category: Tolia NH]] | |||
Latest revision as of 12:33, 17 October 2024
Crystal structure of potently neutralizing human monoclonal antibody 42D6 Fab in complex with MSP1-19Crystal structure of potently neutralizing human monoclonal antibody 42D6 Fab in complex with MSP1-19
Structural highlights
Publication Abstract from PubMedDefining mechanisms of pathogen immune evasion and neutralization are critical to develop potent vaccines and therapies. Merozoite Surface Protein 1 (MSP-1) is a malaria vaccine antigen and antibodies to MSP-1 are associated with protection from disease. However, MSP-1-based vaccines performed poorly in clinical trials in part due to a limited understanding of the protective antibody response to MSP-1 and of immune evasion by antigenic diversion. Antigenic diversion was identified as a mechanism wherein parasite neutralization by a MSP-1-specific rodent antibody was disrupted by MSP-1-specific non-inhibitory blocking/interfering antibodies. Here, we investigated a panel of MSP-1-specific naturally acquired human monoclonal antibodies (hmAbs). Structures of multiple hmAbs with diverse neutralizing potential in complex with MSP-1 revealed the epitope of a potent strain-transcending hmAb. This neutralizing epitope overlaps with the epitopes of high-affinity non-neutralizing hmAbs. Strikingly, the non-neutralizing hmAbs outcompete the neutralizing hmAb enabling parasite survival. These findings demonstrate the structural and mechanistic basis for a generalizable pathogen immune evasion mechanism through neutralizing and interfering human antibodies elicited by antigenic diversion, and provides insights required to develop potent and durable malaria interventions. Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion.,Patel PN, Dickey TH, Hopp CS, Diouf A, Tang WK, Long CA, Miura K, Crompton PD, Tolia NH Nat Commun. 2022 Oct 6;13(1):5888. doi: 10.1038/s41467-022-33336-3. PMID:36202833[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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