Structural model of a complex between the heterotrimeric G protein, Gsalpha, 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 Gsalpha, have been shown to interact strongly with tubulin. Binding of Galpha to tubulin results in increased dynamicity of microtubules due to activation of GTPase of tubulin. Tubulin also activates Gsalpha via a direct transfer of GTP between these molecules. Structural insight into the interaction between tubulin and Gsalpha 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, alpha2-beta4 (the region between switch II and switch III) and alpha3-beta5 (just distal to the switch III region) domains of Gsalpha 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/Gbetagamma interaction regions of Gsalpha and the exchangeable nucleotide-binding site of tubulin. These structural models explain the ability of tubulin to facilitate GTP exchange on Galpha and the ability of Galpha to activate tubulin GTPase.
Layden
Brian T
BT
Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Saengsawang
Witchuda
W
Donati
Robert J
RJ
Yang
Shuo
S
Mulhearn
Debbie C
DC
Johnson
Michael E
ME
Rasenick
Mark M
MM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D014404:Tubulin / Q000378:metabolism*
D010446:Peptide Fragments; D014404:Tubulin; D006160:Guanosine Triphosphate; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases