| Literature References | 1. WALTER, M.R., WINDSOR, W.T., NAGABHUSHAN, T.L., LUNDELL, D.J.,
LUNN, C.A., ZAUODNY, P.J. AND NARULA, S.K.
Crystal structure of a complex between interferon-gamma and its
soluble high-affinity receptor.
NATURE 376 230-235 (1995).
2. SOGABE, S., STUART, F., HENKE, C., BRIDGES, A., WILLIAMS, G.,
BIRCH, A., WINKLER, F.K. AND ROBINSON, J.A.
Neutralizing epitopes on the extracellular interferon gamma receptor
X-ray crystal structure of the A6 fab-IFNgammaR1-108 complex.
J.MOL.BIOL. 273 882-897 (1997).
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| Documentation | Interferon (INF)-gamma is a dimeric glycoprotein produced by activated T
cells and natural killer cells. Although originally isolated based on its
antiviral activity, INF-gamma also displays powerful anti-proliferative and
immuno-modulatory activities, which are essential for developing appropriate
cellular defenses against a variety of infectious agents. The first step in
eliciting these responses is the specific high affinity interaction of INF-
gamma with its cell-surface receptor (INF-gammaRalpha); the complex then
interacts with at least one of a family of additional species-specific
accessory factors (AF-1 or INF-gammabeta), which convey different cellular
responses. One such response is the association and phosphorylation of two
protein tyrosine kinases (Jak-1 and Jak-2), which in turn stimulate nuclear
transcription activators [1].
The human INF-gammaR, is a member of the hematopoietic cytokine receptor
superfamily. It is expressed in a membrane-bound form in many cell types,
and is over-expressed in tumour cells. It comprises an extracellular portion
of 229 residues, a single transmembrane region, and a cytoplasmic domain of
221 residues. As with other members of its superfamily, the cytokine-binding
sites are formed by a small set of closely-spaced surface loops that extend
from a beta-sheet core, much like antigen-binding sites on antibodies. The
extracellular INF-gammaR monomer comprises two domains (domain D1 from
residue 14-102, and domain D2 from residue 114-221), each resembling an Ig
fold with fibronectin type III topology [2].
INGRECEPTOR is a 5-element fingerprint that provides a signature for the
interferon-gamma receptor alpha chains. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length - motif 1 includes
beta-strand 6 in the putative extracellular domain; and motifs 2-5 span the
cytoplasmic domain. A single iteration on SPTR39_17f was required to reach
convergence, no further sequences being identified beyond the starting set.
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