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Structure of the Pf12 and Pf41 heterodimeric complex of <i>Plasmodium falciparum</i> 6-cysteine proteins.

Dietrich MH, Chan LJ, Adair A, Boulet C, O'Neill MT, Tan LL, Keremane S, Mok YF, Lo AW, Gilson P, Tham WH

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  • Journal FEMS microbes

  • Published 16 Feb 2022

  • Volume 3

  • Pagination xtac005

  • DOI 10.1093/femsmc/xtac005

Abstract

proteins usually found on the parasite surface of late schizonts and merozoites. Our structure revealed two critical interfaces required for complex formation with important implications on how different 6-cysteine proteins may interact with each other. Using structure-function analyses, we identified important residues for Pf12-Pf41 complex formation. In addition, we generated 16 nanobodies against Pf12 and Pf41 and showed that several Pf12-specific nanobodies inhibit Pf12-Pf41 complex formation. Using X-ray crystallography, we were able to describe the structural mechanism of an inhibitory nanobody in blocking Pf12-Pf41 complex formation. Future studies using these inhibitory nanobodies will be useful to determine the functional role of these two 6-cys proteins in malaria parasites.