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(Received for publication, May 2, 1995) From the Each G protein-coupled receptor can interact only with a limited
number of the many structurally similar G proteins expressed within a
cell. This study was undertaken to identify single amino acids required
for selectively coupling the m3 muscarinic acetylcholine receptor to G
proteins of the G
Volume 270,
Number 30,
Issue of July 28, pp. 17741-17748, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
by the m3 Muscarinic Acetylcholine Receptor
family. To this goal, distinct
intracellular segments/amino acids of the m3 receptor were
systematically substituted into the structurally closely related m2
muscarinic receptor, which couples to G
proteins, not
G
proteins. The resultant mutant receptors were
expressed in COS-7 cells and studied for their ability to induce
agonist-dependent stimulation of phosphatidylinositol hydrolysis, a
response known to be mediated by G proteins of the G
class. Using this approach, we were able to identify four amino
acids in the second intracellular loop and four amino acids at the C
terminus of the third intracellular loop of the m3 muscarinic receptor
that are essential for efficient G
activation. We could
demonstrate that these amino acids, together with a short segment at
the N terminus of the third intracellular loop, fully account for the G
protein coupling preference of the m3 muscarinic receptor. Taken
together, our data strongly suggest that only a limited number of amino
acids, located on different intracellular regions, are required to
determine the functional profile of a given G protein-coupled receptor.
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