| Literature References | 1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
2. ATTWOOD, T.K. AND FINDLAY, J.B.C.
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
5. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
6. KERLAVAGE, A.R., FRASER, C.M., CHUNG, F-Z. AND VENTER, J.C.
Molecular structure and evolution of adrenergic and cholinergic receptors.
PROTEINS 1 287-301 (1986).
7. WATSON, S. AND ARKINSTALL, S.
Acetylcholine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.7-18.
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| Documentation | G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the
sequence level, on the basis of which they can be separated into distinct
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,
but between which there is no statistically significant similarity in
sequence [1]. The currently known clan members include the rhodopsin-like
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
The rhodopsin-like GPCRs themselves represent a widespread protein family
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary
widely in structure and character, the amino acid sequences of the
receptors are very similar and are believed to adopt a common structural
framework comprising 7 transmembrane (TM) helices [3-5].
The muscarinic acetylcholine receptors, present in the central nervous
system, spinal cord motoneurons and autonomic preganglia, modulate a
variety of physiological functions, including airway, eye and intestinal
smooth muscle contractions; heart rate; and glandular secretions. The
receptors mediate adenylate cyclase attenuation, calcium and potassium
channel activation, and phosphatidyl inositol turnover [6]. This diversity
may result from the occurrence of multiple receptor subtypes (of which 5
are currently known, designated M1 to M5), which have been classified
based on observed differences in ligand binding to receptors in membranes
from several tissues.
The M3 receptor is found in high levels in neuronal cells of the CNS [7];
its distribution largely overlaps with that of M1 and M4 subtypes. It is
also found in peripheral ganglia, exocrine glands, smooth muscle, vascular
endothelium, and in cell lines. No selective agonist has been described [7].
MUSCRINICM3R is a 7-element fingerprint that provides a signature for the
muscarinic M3 receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the M3 receptors but distinguish them
from the rest of the muscarinic receptor family - motif 1 lies at the N-
terminus; motifs 2-6 span the third cytoplasmic loop; and motif 7 lies
at the C-terminus. Two iterations on OWL28.0 were required to reach
convergence, at which point a true set comprising 6 sequences was
identified. A single partial match was also found, BOVMRM3SUB, an M3
receptor fragment.
An update on SPTR37_9f identified a true set of 5 sequences.
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