8dfh | pdb_00008dfh

Crystal structure of non-neutralizing / interfering human monoclonal antibody 42C3 Fab in complex with MSP1-19

spinqualitylabelsall models 8dfh, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dfh is a 3 chain structure with sequence from Homo sapiens and Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8I0U8_PLAF7 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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