Fig. 2
From: The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy
Mapping of reported variants onto 3D structure of tubulin alpha-1A. a TUBA1A (light blue) monomer in the center surrounded by TUBA1A monomers to the lateral sides and TUBB3 monomers to the longitudinal sides (transparent surfaces). The TUBA1A (light blue) - TUBB3 (grey) heterodimer is highlighted and shown in ribbon representation (based on PDB: 5JCO [28]). Exemplary for a motor protein KIF1A (green; PDB: 2HXF [73]) is shown interacting on the external surface. Mutated residues are shown in spheres and likely affect the binding of MAPs or motor proteins (red), tubulin folding (black), intradimer interactions (yellow), longitudinal interactions (magenta), lateral interactions (green) or GTP-binding pocket (beige). Variants on the luminal side are shown in blue. A cross section and longitudinal view of a microtubule [74] is provided for orientation. b Close-up view of the central TUBA1A monomer and c lateral-view with TUBB3 removed from the dimer. The GTP molecule (beige), required for polymerization, is presented in stick representation. Variants identified in the three individuals i084n (P173L), i085n (G436D), i086n (R214H) described here affect tubulin folding, MAP binding and intradimer interaction, respectively. d Simplified representation of TUBA1A and KIF1A with protein surface and spheres removed. The amino acid residue R402 (red stick representation) of TUBA1A is localized near the KIF1A protein, in particular to the amino acid residue K280 (minimal distance 1.9 Å; green stick representation)