Figure 5 | Scientific Reports

Figure 5

From: Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration

Figure 5

Structural modelling of the impact of variants in the gC1Q domain of C1QTNF5 upon folding and assembly of the monomer, trimer and octadecamer. (a) Structure of the C1QTNF5 gC1q domain homotrimer (PDB ID: 4F3J)11, with the locations of the pathogenic (red) and ExAC missense variants (blue) highlighted. (b) Structure of the C1QTNF5 gC1q domain 18-mer (PDB ID: 4NN0)12, with the locations of the pathogenic (red) and ExAC missense variants (blue) highlighted. (c) Comparison of the predicted effects on protein folding (pink) and assembly of trimers (green) and higher-order complexes (orange) for the pathogenic and ExAC amino acid substitutions. The total destabilisation, equal to the sum of the effect on folding and assembly, is shown as a red or blue dot for each substitution. The pathogenic substitutions are significantly more destabilizing than those in ExAC (p = 0.002, Wilcoxon rank-sum test).

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