Figure 4.

Structural organization of amino acid conservation across K13 KREP. (a) Structure-based amino acid alignment of the six blade (or kelch) repeats of PfK13 KREP. The x axis shows the position in the structure-based amino acid alignment of the six blades; the left y axis shows the amino acid blade number, followed by the first and last amino acid (AA) positions of the corresponding blade. The strands of PfK13 KREP are colored in grey; the AB and CD loops forming the top face of the KREP are colored in cyan; the BC and DA loops architecting the bottom face of the KREP are colored in yellow and green respectively. A consensus sequence of the blades was defined and is shown below the alignment: strict consensus amino acids are shown in bold capital letters and highly conserved amino acids are shown in standard lowercase. A mapping of the different strands and loops onto the three-dimensional structure of PfK13 KREP is shown as surface representation above the structure-based amino acid alignment: side view (left), bottom view (middle) and top view (right). The outline of the shallow pocket surface was delineated with a black line on the bottom view structure (middle) and the amino acid sites forming the shallow pocket surface were surrounded and written in bold in the structure-based amino acid alignment. (b) Mapping of the site-specific substitution rates λ onto the structure-based amino acid alignment of the six blade repeats of PfK13 KREP. Upper graph: heat map showing the λ substitution rate for each amino acid site. Black boxes correspond to the gaps in the structure-based amino acid alignment. The median of the λ substitution rates was first calculated (white) to produce a scale ranging from the lowest (magenta) to the highest (green) site-specific substitution rate λ. Lower graph: Plot of the mean and 95% confidence interval of the λ substitution rates along the structure-based amino acid alignment of the six blades. The positions including one or more gaps were discarded.