| 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. WATSON, S. AND ARKINSTALL, S.
Bombesin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.60-66.
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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].
Bombesins are peptide neurotransmitters whose biological activity resides
in a common C-terminal sequence, WAXGHXM [6]. In the periphery, bombesin-
related peptides stimulate smooth muscle and glandular secretion. In the
brain, these peptides are believed to play a role in homeostasis, thermo-
regulation and metabolism, and have been reported to elicit analgesia and
excessive grooming, together with central regulation of a variety of
peripheral effects.
Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript
encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The
preproNMB gene transcript encodes a precursor of 117 amino acids, which is
metabolised to neuromedin B. Receptors for these peptides have widespread
distribution in peripheral tissue. High levels are found in smooth muscle
and in the brain.
BOMBESINR is a 6-element fingerprint that provides a signature for the
bombesin receptors. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved sections within either
loop or TM regions, focusing on those areas of the alignment that
characterise the bombesin receptors but distinguish them from the rest of
the rhodopsin-like superfamily - motif 1 spans the C-terminus of TM domain
2 leading into the first external loop; motif 2 lies in the N-terminal
region of TM domain 3; motif 3 spans part of the second external loop;
motif 4 was taken from the third cytoplasmic loop; motif 5 spans part of
the third external loop leading into TM domain 7; and motif 6 lies at the
C-terminus. Two iterations on OWL26.0 were required to reach convergence,
at which point a true set comprising 7 sequences was identfied.
An update on SPTR37_9f identified a true set of 9 sequences, and 2
partial matches.
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