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기타논문
Date: 12 December 2003
Journal: Journal of Biological Chemistry Volume 278, Issue 50, 12 December 2003, Pages 50530-50536 , Doi: 10.1074/jbc.M304417200
2003 | Closely Related G-protein-coupled Receptors Use Multiple and Distinct Domains on G-protein α-Subunits <b class="sch_word">for</b> Selective Coupling…
- Slessareva, J.E.ac, Ma, H.ad, Depree, K.M.a, Flood, L.A.a, Bae, H.b, Cabrera-Vera, T.M.b, Hamm, H.E.be, Graber, S.G.af
첨부파일
Abstract
The molecular basis of selectivity in G-protein receptor coupling has been explored by comparing the abilities of G-protein heterotrimers containing chimeric Gα subunits, comprised of various regions of G i1α, Gtα, and Gqα, to stabilize the high affinity agonist binding state of serotonin, adenosine, and muscarinic receptors. The data indicate that multiple and distinct determinants of selectivity exist for individual receptors. While the A1 adenosine receptor does not distinguish between Gi1α and Gtα sequences, the 5-HT1A and 5-HT1B serotonin and M2 muscarinic receptors can couple with Gi1 but not Gt. It is possible to distinguish domains that eliminate coupling and are defined as "critical," from those that impair coupling and are defined as "important." Domains within the N terminus, α4-helix, and α4-helix-α4/β6-loop of Gi1α are involved in 5-HT and M2 receptor interactions. Chimeric Gi1α/G qα subunits verify the critical role of the Gα C terminus in receptor coupling, however, the individual receptors differ in the C-terminal amino acids required for coupling. Furthermore, the EC50 for interactions with Gi1 differ among the individual receptors. These results suggest that coupling selectivity ultimately involves subtle and cooperative interactions among various domains on both the G-protein and the associated receptor as well as the G-protein concentration.
Indexed keywords
Engineering controlled terms: Amino acids; Proteins
Engineering uncontrolled terms: Impair coupling
Engineering main heading: Biochemistry
EMTREE drug terms: adenosine receptor; cell surface receptor; G protein coupled receptor; guanine nucleotide binding protein; muscarinic receptor; protein subunit; serotonin receptor
EMTREE medical terms: alpha chain; alpha helix; amino acid sequence; animal cell; article; binding affinity; chimera; coupling factor; molecular interaction; molecular recognition; nonhuman; priority journal; protein analysis; protein domain; protein purification; receptor affinity; receptor binding
MeSH: Amino Acid Sequence; Animals; Cell Line; Cell Membrane; Dimerization; Dose-Response Relationship, Drug; GTP-Binding Protein alpha Subunits, Gi-Go; GTP-Binding Protein alpha Subunits, Gq-G11; Insects; Models, Molecular; Molecular Sequence Data; Mutation; Point Mutation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Radioligand Assay; Sequence Homology, Amino Acid; Transducin
Medline is the source for the MeSH terms of this document.
Species Index: Animalia
Chemicals and CAS Registry Numbers: GTP-Binding Protein alpha Subunits, Gi-Go, EC 3.6.1.46; GTP-Binding Protein alpha Subunits, Gq-G11, EC 3.6.1.46; Transducin, EC 3.6.1.-