RGD Reference Report - TM2-TM7 interaction in coupling movement of transmembrane helices to activation of the angiotensin II type-1 receptor. - Rat Genome Database

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TM2-TM7 interaction in coupling movement of transmembrane helices to activation of the angiotensin II type-1 receptor.

Authors: Miura, S  Zhang, J  Boros, J  Karnik, SS 
Citation: Miura S, etal., J Biol Chem 2003 Feb 7;278(6):3720-5.
RGD ID: 629553
Pubmed: PMID:12446719   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M211338200   (Journal Full-text)

Agonist-induced rigid body motion of transmembrane (TM) helices has been established as a unifying mechanism in the activation of the G protein-coupled receptors. In attempts to measure specific conformational transitions during the activation of the type 1 receptor for angiotensin II (AT(1)), we found a decrease in accessibility of Cys(76) in the second TM helix, suggesting that the orientation of TM2 is altered (Miura, S., and Karnik, S. S. (2002) J. Biol. Chem. 277, 24299-24305). Now we provide evidence that the TM2 helical movement plays a role in regulating the activated state of the AT(1) receptor, and this role may involve an interaction between TM2 and TM7. Alanine substitution of native Cys(296) in TM7 leads to increased accessibility of Cys(289) and diminished response to bound agonist. Both effects of the C296A mutation are suppressed when combined with F77A and N111G mutants. The TM7 conformation and the sensitivity of Cys(289) altered by C296A mutation are suppressed by the F77A mutation in TM2 to salvage function. We show that the F77A mutant alters orientation of both TM2 and TM7 but does not induce constitutive activity in suppressing the C296A mutant effects. Thus, interaction of TM2 and TM7 is important for transmembrane signal transduction in the AT(1) receptor.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
G protein-coupled receptor signaling pathway  IMP 629553; 629553 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiac hypertrophy  TAS 629553 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)

Genes (Mus musculus)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Homo sapiens)
AGTR1  (angiotensin II receptor type 1)

Objects referenced in this article
Gene Agtr1b angiotensin II receptor, type 1b Mus musculus

Additional Information