Structural model of a complex between the heterotrimeric G protein, Gsα, and tubulin
| Autor: | Mark M. Rasenick, Witchuda Saengsawang, Brian T. Layden, Robert J. Donati, Michael E. Johnson, Shuo Yang, Debbie C. Mulhearn |
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| Rok vydání: | 2008 |
| Předmět: |
Gs alpha subunit
Protein Conformation G protein Molecular Sequence Data Microtubule macromolecular substances GTPase Biology Microtubules Article Adenylyl cyclase chemistry.chemical_compound Tubulin Heterotrimeric G protein GTP-Binding Protein alpha Subunits Gs Animals Amino Acid Sequence Cytoskeleton Molecular Biology Sheep Sequence Homology Amino Acid Crystal structure Cell Membrane Brain Cell Biology Peptide Fragments Protein Structure Tertiary Cell biology Models Chemical chemistry biology.protein Guanosine Triphosphate Adenylyl Cyclases |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783(6):964-973 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2008.02.017 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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