Fig. 1

Integrative protein structure modeling for four variants identified in individuals with childhood cataracts. Affected amino acids are highlighted in red. a, b Models of the CRYBA1 c.272_274del, p. (Gly91del) (a) and CRYBA4 c.136_156del, p. (Ser46_Gly52del) (b) variants. The CRYBA1 and CRYBA4 proteins exhibit significant sequence similarity and the template with pdb code 3LWK (human β-crystallin A4) was used on both occasions. The main chain backbone atoms (white/grey lines) and the hydrogen bond network (brown lines) of the affected protein regions are shown. Both sequence alterations involve deleting residues located in β-sheets. c Homology model of the BFSP2 c.697_699del, p. (Glu233del) variant. BFSP2 forms parallel coiled-coil dimers that interact with one another in the form of a symmetrical anti-parallel dimer. The main chain backbone atoms (white/yellow lines) and the side chains that comprise the interaction interface (green) of the affected protein region are shown. The wild-type protein is presented on the left hand-side image. Notably, the affected amino acid is located in an α-helical region (highlighted in red). The right hand-side image shows a model of the mutant protein; the deletion shifts the position of the interacting side chains resulting in disruption of the dimer structure and exposure of the hydrophobic interface residues to the protein surface. d Model of the PITX2 c.429_431del, p. (Arg144del) variant. The main chain backbone atoms of the protein (white/grey lines) complexed with an interacting DNA double helix (brown chain) are shown. The mutated residue (highlighted in red) makes direct contact with the phosphate backbone of DNA, forming a salt bridge