| 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. HOLMES, W.E., LEE, J., KUANG, W-J., RICE, G.C. AND WOOD, W.I.
Structure and functional expression of a human interleukin-8 receptor.
SCIENCE 253 1278-1280 (1991).
7. MOLLEREAU, C., MUSCATELLI, F., MATTEI, M.G., VASSART, G. AND
PARMENTIER, M.
The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36
region of the human genome: cloning of a pseudogene (IL8RBP) for the
low-affinity receptor.
GENOMICS 16 248-251 (1993).
8. BAGGIOLINI, M. AND CLARK-LEWIS, I.
Interleukin-8, a chemotactic and inflammatory cytokine.
FEBS LETT. 307 97-101 (1992).
9. WATSON, S. AND ARKINSTALL, S.
Chemokines.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.83-88.
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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].
Interleukin-8 (IL8) is a pro-inflammatory cytokine involved in the cellular
response to inflammation, being a powerful chemoattractant for neutrophils
[6]. There are 2 similar cell surface receptors for IL8: type 1 (IL-8RA) is
a high affinity receptor for IL8 alone; while type 2 (IL-8RB) is a high
affinity receptor for IL8, growth related gene (GRO) and neutrophil-
activating protein-2 (NAP-2). The affinity of type 1 receptors for IL8 is
higher than that of type 2 receptors [6,7]. The receptors are coupled to
Bordetella pertussis toxin-sensitive GTP-binding proteins [8]. Signal
transduction depends on the activation of a phospholipase C specific for
phosphatidylinositol-4,5-bisphosphate, producing 2 second messengers:
inositol triphosphate and diacylglycerol [8]. Inositol triphosphate induces
a rise in the levels of cytosolic free calcium, while diacylglycerol
activates protein kinase C, leading to activation of neutrophils [8].
IL8RB receptors are found in high density in neutrophils, monocytes,
basophils, and melanoma cells, and in lower density in T-cells [9]. IL8
has been reported to stimulate the phosphoinositide pathway through an
uncharacterised G protein; pertussis toxin also inhibits several of its
actions [9]. The IL8RB receptor shares around 80% similarity with the
IL8RA receptor.
INTRLEUKN8AR is a 4-element fingerprint that provides a signature for the
interleukin 8B receptors. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved sections
within both N- and C-terminal regions, focusing on those areas of the
alignment that characterise the interleukin 8B receptors but distinguish
them from the rest of the rhodopsin-like superfamily - motifs 1 and 2 lie
at the N-terminus; and motifs 3 and 4 lie at the C-terminus. A single
iteration on OWL28.1 was required to reach convergence, no further
sequences being identified beyond the starting set.
An update on SPTR37_9f identified a true set of 4 sequences.
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