| Based on our experimental data, the X-ray structure of the mature Ab, and MD simulations, we propose the model shown above for how 4-4-20 evolved for biological function. Mutations were first selected in the Ab heavy chain (blue), localized to two clusters: a 'binding site' cluster involving the CDR1 and CDR2 loops that form one wall of the combining site and a 'distal cluster' that is >20 Å removed from the combining site. Mutations were then selected in the light chain (red) to optimize hydrogen bonding within the conformation selected by the heavy chain mutations. |
