Human Germline Antibody Gene Segments Encode Polyspecific Antibodies
Figure 3
Phi-psi variances for framework residues.
The degree of structural variation of the framework residues were measured as the standard deviation of the phi and psi angles over each residue position. (A) Side view of immunoglobulin fold for VH5-51 complexes aligned by framework residues. Beta-sheets included in the analysis are shown as a cartoon representation, while loop regions are in a transparent ribbon representation. Framework 1 is shown in brown, CDR 1 in green, framework 2 in black, CDR 2 in magenta, and framework 3 in cyan. (B) Top down view. (C) The standard deviations of the phi-psi angles of each framework position were binned into either a residue that was found to be critical for polyspecificity (recovered to germline) or a residue that was not recovered to germline in multi-state design. For each position, the phi-psi angles were averaged, and the standard error of the mean was calculated. An average of 19.6°±2.0° for germline recovered residues and 15.47°±1.5° for non-germline recovered residues supporting our hypothesis that residues which enable polyspecificity alter beta-sheet packing to a greater degree than residues that do not. The axis is normalized to 18.7°±0.9°, the average deviation for all beta-sheet framework positions.