4R3S

Crystal Structure of anti-MSP2 Fv fragment (mAb6D8)in complex with MSP2 11-23

Summary for 4R3S

• Entry DOI: 10.2210/pdb4r3s/pdb
• Related: 4QXT 4QY8 4QYO
• Descriptor: FV FRAGMENT(MAB6D8) HEAVY CHAIN, FV FRAGMENT(MAB6D8) LIGHT CHAIN, Merozoite surface protein, ... (4 entities in total)
• Functional Keywords: immunoglobulin fold, n-terminal msp2, unstructured antigen, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 26060.82

Authors

Morales, R.A.V.,MacRaild, C.A.,Seow, J.,Bankala, K.,Drinkwater, N.,McGowan, S.,Rouet, R.,Christ, D.,Anders, R.F.,Norton, R.S. (deposition date: 2014-08-18, release date: 2015-06-03, Last modification date: 2024-10-30)

Primary citation

Morales, R.A.V.,MacRaild, C.A.,Seow, J.,Krishnarjuna, B.,Drinkwater, N.,Rouet, R.,Anders, R.F.,Christ, D.,McGowan, S.,Norton, R.S.
Structural basis for epitope masking and strain specificity of a conserved epitope in an intrinsically disordered malaria vaccine candidate
Sci Rep, 5:10103-10103, 2015

PubMed Abstract: Merozoite surface protein 2 (MSP2) is an intrinsically disordered, membrane-anchored antigen of the malaria parasite Plasmodium falciparum. MSP2 can elicit a protective, albeit strain-specific, antibody response in humans. Antibodies are generated to the conserved N- and C-terminal regions but many of these react poorly with the native antigen on the parasite surface. Here we demonstrate that recognition of a conserved N-terminal epitope by mAb 6D8 is incompatible with the membrane-bound conformation of that region, suggesting a mechanism by which native MSP2 escapes antibody recognition. Furthermore, crystal structures and NMR spectroscopy identify transient, strain-specific interactions between the 6D8 antibody and regions of MSP2 beyond the conserved epitope. These interactions account for the differential affinity of 6D8 for the two allelic families of MSP2, even though 6D8 binds to a fully conserved epitope. These results highlight unappreciated mechanisms that may modulate the specificity and efficacy of immune responses towards disordered antigens.

PubMed: 25965408
DOI: 10.1038/srep10103

Experimental method

X-RAY DIFFRACTION (1.7 Å)