Fig. 6

A, B 3D model of SQSTM1. AlphaFold 2 model for SQSTM1 (A). In addition to the structure of already known domains PB1 (amino acid 3–102), Zinc finger (122–168) and UBA (375–439), folding of SQSTM1 by AlphaFold 2 showed a new domain named Serum response factor-transcription factor (SRF-TF)-like (amino acid 232–268). AlphaFold 2 produced a per-residue confidence score (pLDDT) between 0 and 100: in blue, very high (pLDDT > 90); in cyan, confident (90 > pLDDT > 70); in yellow, low (70 > pLDDT > 50) and in orange, very low (pLDDT < 50). Some regions below 50 pLDDT may be unstructured in isolation. Diagram representation of SQSTM1 colored by domain (B) generated by http://ibs.biocuckoo.org/online.php#. C–E Prediction of the effect of the p.Pro392Leu mutation in stability and dynamics of SQSTM1 by DynaMut. The change in vibrational entropy energy of the UBA domain is colored based on the effect of the p.Pro392Leu mutation (C). The UBA domain is in blue that represents a rigidification of the structure relatively to the wild type. The predicted interatomic interactions for Pro392 (D) and Leu392 (E) residues are shown as sticks and colored in light green along with surrounding residues that are involved in any type of interactions. The p.Pro392Leu mutation created hydrophobic bonds (green dashes) between Leu392 and Pro374 (E). F, G 3D model of DOCK6. AlphaFold 2 model for DOCK6 (F). The p.Val45Ile variant is localized in N-terminal of DOCK6. This domain is mainly intrinsically disordered (regions in orange that are below 50 per-residue confidence score (pLDDT) may be unstructured in isolation). AlphaFold 2 produces a per-residue confidence score (pLDDT) between 0 and 100: in blue, very high (pLDDT > 90); in cyan, confident (90 > pLDDT > 70); in yellow, low (70 > pLDDT > 50) and in orange, very low (pLDDT < 50). Some regions below 50 pLDDT may be unstructured in isolation. Diagram representation of DOCK6 colored by domain (G) generated by http://ibs.biocuckoo.org/online.php#