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Structural basis of Plasmodium vivax inhibition by antibodies binding to the circumsporozoite protein repeats.
- Source :
-
ELife [Elife] 2022 Jan 13; Vol. 11. Date of Electronic Publication: 2022 Jan 13. - Publication Year :
- 2022
-
Abstract
- Malaria is a global health burden, with Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) responsible for the majority of infections worldwide. Circumsporozoite protein (CSP) is the most abundant protein on the surface of Plasmodium sporozoites, and antibodies targeting the central repeat region of CSP can prevent parasite infection. Although much has been uncovered about the molecular basis of antibody recognition of the PfCSP repeats, data remains scarce for PvCSP. Here, we performed molecular dynamics simulations for peptides comprising the PvCSP repeats from strains VK210 and VK247 to reveal how the PvCSP central repeats are highly disordered, with minor propensities to adopt turn conformations. Next, we solved eight crystal structures to unveil the interactions of two inhibitory monoclonal antibodies (mAbs), 2F2 and 2E10.E9, with PvCSP repeats. Both antibodies can accommodate subtle sequence variances in the repeat motifs and recognize largely coiled peptide conformations that also contain isolated turns. Our structural studies uncover various degrees of Fab-Fab homotypic interactions upon recognition of the PvCSP central repeats by these two inhibitory mAbs, similar to potent mAbs against PfCSP. These findings augment our understanding of host -Plasmodium interactions and contribute molecular details of Pv inhibition by mAbs to unlock structure-based engineering of PvCSP-based vaccines.<br />Competing Interests: IK, LH, DI, QY, JR, RP, JJ No competing interests declared<br /> (© 2022, Kucharska et al.)
- Subjects :
- Animals
Antibodies, Protozoan chemistry
Cell Line
Crystallization
HEK293 Cells
Humans
Mice
Protozoan Proteins chemistry
Protozoan Proteins genetics
Sporozoites metabolism
Antibodies, Protozoan metabolism
Binding Sites, Antibody
Molecular Dynamics Simulation
Plasmodium vivax immunology
Plasmodium vivax metabolism
Protozoan Proteins immunology
Protozoan Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 11
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 35023832
- Full Text :
- https://doi.org/10.7554/eLife.72908