A GPR-Protein Interaction Surface of Giα: Implications for the Mechanism of GDP-Release Inhibition
| Autor: | Michael Natochin, Nikolai O. Artemyev, Karim G. Gasimov |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Stereochemistry
GTP-Binding Protein alpha Subunits Amino Acid Motifs Alpha (ethology) GTPase Plasma protein binding GTP-Binding Protein alpha Subunits Gi-Go Binding Competitive Guanosine Diphosphate Biochemistry GTP-Binding Protein Regulators Animals Guanine Nucleotide Exchange Factors Trypsin Cloning Molecular Guanine Nucleotide Dissociation Inhibitors Chimera Chemistry Neuropeptides fungi Precipitin Tests Fusion protein Rats A-site Guanosine 5'-O-(3-Thiotriphosphate) Cattle Guanosine Triphosphate Guanine nucleotide exchange factor Carrier Proteins Protein Binding |
| Zdroj: | Biochemistry. 41:258-265 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi015708k |
| Popis: | Proteins containing G-protein regulatory (GPR) motifs represent a novel family of guanine nucleotide dissociation inhibitors (GDIs) for G(alpha) subunits from the Gi family. They selectively interact with the GDP-bound conformation of Gi(alpha) and transducin-alpha (Gt(alpha)), but not with Gs(alpha). A series of chimeric proteins between Gi(alpha)(1) and Gs(alpha) has been constructed to investigate GPR-contact sites on G(alpha) subunits and the mechanism of GPR-protein GDI activity. Analysis of the interaction of two GPR-proteins-AGS3GPR and Pcp2-with the chimeric G(alpha) subunits demonstrated that the GPR-Gi(alpha)(1) interface involves the Gi(alpha)(1) switch regions and Gi(alpha)(1)-144-151, a site within the helical domain. Residues within Gi(alpha)(1)-144-151 form conformation-sensitive contacts with switch III, and may directly interact with a GPR-protein or form a GPR-binding surface jointly with switch III. The helical domain site is critical to the ability of GPR-proteins to act as GDIs. Our data suggest that a mechanism of the GDI activity of GPR-proteins is different from that of GDIs for monomeric GTPases and from the GDI-like activity of G(betagamma) subunits. The GPR-proteins are likely to block a GDP-escape route on G(alpha) subunits. |
| Databáze: | OpenAIRE |
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