Figure 5
Structural considerations of the RAC1 variants. (a) Crystal structure of the human RAC3-PAK1 complex (PDB: 2QME) and close-up views of the region around Tyr40 for the wild type and the His40 variant model of RAC3. RAC3 and PAK1 in the complex are represented by green and cyan cartoons, respectively; the Switch I (Thr25–Asn39) and the Switch II (Asp57–Gln74) regions of RAC3 are shown in purple and beige, respectively. A non-hydrolyzable analog of GTP, phosphomethylphosphonic acid-guanylate ester (GCP), and the Mg2+ ion are shown as yellow sticks and a gray ball, respectively. (middle) Variant residue Tyr40 and the residues forming a hydrophobic core are shown as van der Waals spheres. Oxygen and nitrogen atoms are shown in red and blue, respectively. The dotted line represents a hydrogen bond (right). Structural model of the p.Tyr40His variant of RAC3 predicted by FoldX. (b) The complex structure from another angle and close-up views of the region around Asn39 of the wild type and the Ser39 variant model of RAC3 (middle and right). The variant residue Asn39, the modeled Ser39, and the residues forming hydrogen bonds with these residues are shown as sticks. Trp56, which makes van der Waals contacts with Asn39, is shown as a translucent sphere. Molecular structures were drawn using PyMOL Ver 2.5 (http://www.pymol.org). (c) The free energy changes for the indicated variants calculated by FoldX.
