Fig. 2: Analysis of Pfs230D1M-Fab structure and polymorphisms.

a Two views of the structure of Pfs230D1 complexed with the 4F12 Fab. Pfs230D1 (magenta) shown as a ribbon diagram bound to the light (cyan) and heavy (green) chains. The views are separated by 90 degrees around the vertical axis. VL, VH, light or heavy chain variable regions. CL, CH light or heavy chain constant domains. N N-terminus. C C-terminus. b Superpositions of 6-cys family members on Pfs230D1. Upper left: Ribbon diagram of Pfs230D1 (magenta) alone. Upper right: Pf12 domain 1 (yellow) on Pfs230D1. Middle left: Pf48/45 domain 3 (green) overlaid on Pfs230D1. Middle right: Pf12 domain 2 (yellow) on Pfs230D1. Lower left: Pf41 domain 1 (gray) on Pfs230D1. Lower right: Pf41 domain 2 (gray) on Pfs230D1. The orientation of Pfs230D1 is identical in all panels. The “C-terminal” ends of the domains where both beta-strands and loops overlay closely are pointing down, at the “bottom” of the domains. The “N-terminal” ends where the loops diverge are at the “top” of the domains. c Location and minor allele frequency (MAF) of the thirteen sequence variants within the crystal structure (lines with arrows) and two variants just outside the structure (lines without arrows). The reference amino-acid G605 identified in NF54 is labelled without a mutation as it was determined to be the minor allele. Bolded residues of low frequency variants (MAF < 0.001) were those with the highest shared occurrence rate. The bolded resides would be likely to appear in the same samples more frequently than others. See text and methods. d Left, surface representation of the Pfs230D1 polymorphisms mapped on to the Pfs230D1 structure. The residues with the highest colocalized occurrence rate are bolded and their surfaces are in blue. The other polymorphisms are denoted in orange on the figure. The residue G605 is in red. For clarity, the labels for A699, D713, and D714 are given twice. Right, Pfs230D1 in surface representation (gray) and Fab 4F12 in ribbon, showing that 4F12 binds to a surface of Pfs230D1 that is not polymorphic. The closest polymorphic residue to the epitope is G605 (red), which does not contact the Fab.