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 alpha subunits of some heterotrimeric G proteins, including Gs alpha, have been shown to interact strongly with tubulin. Binding of G alpha to tubulin results in increased dynamicity of microtubules due to activation of GTPase of tubulin. Tubulin also activates Gs alpha via a direct transfer of GTP between these molecules. Structural insight into the interaction between tubulin and Gs alpha 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, alpha 2-beta 4 (the region between switch II and switch III) and alpha 3-beta 5 (just distal to the switch III region) domains of Gs alpha 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/G beta gamma interaction regions of Gs alpha and the exchangeable nucleotide-binding site of tubulin. These structural models explain the ability of tubulin to facilitate GTP exchange on G alpha and the ability of G alpha to activate tubulin GTPase. (C) 2008 Elsevier B.V. All rights reserved.