Structural model of a complex between the heterotrimeric G protein, Gsα, and tubulin

A number of studies have demonstrated interplay between the cytoskeleton and G protein signaling. Many of these studies have determined a specific interaction between tubulin, the building block of microtubules, and G proteins. The α subunits of some heterotrimeric G proteins, including Gsα, have been shown to interact strongly with tubulin. Binding of Gα to tubulin results in increased dynamicity of microtubules due to activation of GTPase of tubulin. Tubulin also activates Gsα via a direct transfer of GTP between these molecules. Structural insight into the interaction between tubulin and Gsα was required, and was determined, in this report, through biochemical and molecular docking techniques. Solid phase peptide arrays suggested that a portion of the amino terminus, α2-β4 (the region between switch II and switch III) and α3-β5 (just distal to the switch III region) domains of Gsα are important for interaction with tubulin. Molecular docking studies revealed the best-fit models based on the biochemical data, showing an interface between the two molecules that includes the adenylyl cyclase/Gβγ interaction regions of Gsα and the exchangeable nucleotide-binding site of tubulin. These structural models explain the ability of tubulin to facilitate GTP exchange on Gα and the ability of Gα to activate tubulin GTPase.