Substrate-Induced Changes in the Dynamics of Rhodopsin Kinase (G Protein-Coupled Receptor Kinase 1)
| Autor: | Tivadar Orban, Kristoff T. Homan, Krzysztof Palczewski, John J.G. Tesmer, Beata Jastrzebska, Chih Chin Huang |
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| Rok vydání: | 2012 |
| Předmět: |
Rhodopsin
G-Protein-Coupled Receptor Kinase 1 G protein Molecular Conformation Molecular Dynamics Simulation Biochemistry Article chemistry.chemical_compound Adenosine Triphosphate Heterotrimeric G protein Animals Amino Acid Sequence Phosphorylation Cells Cultured G protein-coupled receptor G protein-coupled receptor kinase Sequence Homology Amino Acid biology Kinase Rod Cell Outer Segment Protein Structure Tertiary Rhodopsin kinase chemistry biology.protein Biophysics Cattle Adenosine triphosphate Signal Transduction |
| Zdroj: | Biochemistry. 51:3404-3411 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi300295y |
| Popis: | G protein-coupled receptor (GPCR) kinases (GRKs) instigate the desensitization of activated GPCRs via phosphorylation that promotes interaction with arrestins, thereby preventing the interaction of GPCRs with heterotrimeric G proteins. A current proposed model of GRK1 activation involves the binding of activated rhodopsin (Rho*) to the N-terminal region of GRK1. Perhaps concomitantly, this N-terminal region also stabilizes a closed, active conformation of the kinase domain. To further probe this model, we mapped changes in the backbone flexibility of GRK1 as it binds to its two substrates, adenosine triphosphate (Mg(2+)·ATP) and Rho*. We found that the conformational flexibility of GRK1 was reduced in the presence of either Mg(2+)·ATP or Rho*, with Mg(2+)·ATP having the greatest effect. In a truncated form of GRK1 lacking the N-terminal region (ΔN-GRK1), peptides that directly interact with ATP were not as dramatically stabilized by adding Mg(2+)·ATP, and dynamics were greater in the interface between the large lobe of the kinase domain and the regulator of the G protein signaling homology domain. In the presence of Mg(2+)·ATP, the influence of Rho* versus Rho on GRK1 dynamics was negligible. |
| Databáze: | OpenAIRE |
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