4qxt

Crystal Structure of anti-MSP2 Fv fragment (mAb6D8)in complex with FC27-MSP2 14-30Crystal Structure of anti-MSP2 Fv fragment (mAb6D8)in complex with FC27-MSP2 14-30

Structural highlights

4qxt is a 3 chain structure with sequence from Mus musculus and Plasmodium falciparum K1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.58Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MSA2_PLAFF May play a role in the merozoite attachment to the erythrocyte.^[1]

Publication Abstract from PubMed

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.

Structural basis for epitope masking and strain specificity of a conserved epitope in an intrinsically disordered malaria vaccine candidate.,Morales RA, MacRaild CA, Seow J, Krishnarjuna B, Drinkwater N, Rouet R, Anders RF, Christ D, McGowan S, Norton RS Sci Rep. 2015 May 12;5:10103. doi: 10.1038/srep10103. PMID:25965408^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Boyle MJ, Langer C, Chan JA, Hodder AN, Coppel RL, Anders RF, Beeson JG. Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. Infect Immun. 2014 Mar;82(3):924-36. PMID:24218484 doi:10.1128/IAI.00866-13
↑ Morales RA, MacRaild CA, Seow J, Krishnarjuna B, Drinkwater N, Rouet R, Anders RF, Christ D, McGowan S, Norton RS. Structural basis for epitope masking and strain specificity of a conserved epitope in an intrinsically disordered malaria vaccine candidate. Sci Rep. 2015 May 12;5:10103. doi: 10.1038/srep10103. PMID:25965408 doi:http://dx.doi.org/10.1038/srep10103

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OCA

[1] Boyle MJ, Langer C, Chan JA, Hodder AN, Coppel RL, Anders RF, Beeson JG. Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. Infect Immun. 2014 Mar;82(3):924-36. PMID:24218484 doi:10.1128/IAI.00866-13

[2] Morales RA, MacRaild CA, Seow J, Krishnarjuna B, Drinkwater N, Rouet R, Anders RF, Christ D, McGowan S, Norton RS. Structural basis for epitope masking and strain specificity of a conserved epitope in an intrinsically disordered malaria vaccine candidate. Sci Rep. 2015 May 12;5:10103. doi: 10.1038/srep10103. PMID:25965408 doi:http://dx.doi.org/10.1038/srep10103

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