Figure 2: In silico studies. | Nature Communications

Figure 2: In silico studies.

From: A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li–Fraumeni-like families

Figure 2

(a) Amino acid conservation across representative phylogeny of POT1 orthologues (tet, Tetraodon nigroviridis; xen, Xenopus laevis; gal, Gallus gallus; hum, Homo sapiens; mou, Mus musculus). The mouse POT1a gene sequence was used in the alignment. Position p.117 is shown in blue; mutations described in previous studies are shown in yellow. Triangles indicate positions with putative conformational changes (red) and loss of TPP1-binding site (green) due to the p.R117C mutation. ‘*’ indicates amino acid (aa) conserved in all POT1 orthologues. (b) Heat map representation shows the tolerance to independent aa substitutions (y-axis) for each position of the protein (x-axis). Dark red indicates the highest score for a deleterious effect (score 100); white indicates a small effect; green indicates a neutral effect/no effect (score −100); and black represents the corresponding wild-type residue. Deleteriousness effect score is shown for highlighted positions. (c) Putative tertiary structure. p.152 and p.266 residues change PACC score value driving a putative protein conformation change. Left: homology-based three-dimensional model of human POT1 (Uniprot, Q9NUX5). Right: structural impact of the p.R117C mutation using the same algorithm from Protein Model Portal (Uniprot, PSI_SBKB). Black triangle shows the loop where p.117 is located. Red triangles show the principal detected structural changes (p.152 and p.266). Blue arrows show OB1 and OB2 domains.

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