1fyh
From Proteopedia
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1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR
Contents |
Overview
BACKGROUND: Interferon-gamma (IFN-gamma) is a homodimeric cytokine that, exerts its various activities by inducing the aggregation of two different, receptors. The alpha chain receptor (IFN-gammaRalpha) is a high affinity, receptor that binds to IFN-gamma in a symmetric bivalent manner to form a, stable, intermediate 1:2 complex. This intermediate forms a binding, template for the subsequent binding of two copies of the second receptor, beta chain receptor (IFN-gammaRbeta), producing the active 1:2:2 signaling, complex. RESULTS: A single chain monovalent variant of IFN-gamma, (scIFN-gamma) was constructed and complexed to one copy of the, extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1, complex was determined and the hormone-receptor interface shown to be, characterized by a number of hydrophilic interactions mediated by several, highly ordered water networks. The scIFN-gamma interface consists of, segments from each of the monomer chains of the homodimer. The principal, hydrophobic contact of the receptor involves a tripeptide segment of the, receptor having an unusual and high energy conformation. Despite, containing only one binding site for IFN-gammaRalpha, the monovalent, scIFN-gamma molecule has significant activity in antiviral biological, assays. CONCLUSIONS: ScIFN-gamma binds the ECD of IFN-gammaRalpha through, a highly hydrated interface with an important set of hormone-receptor, contacts mediated through structured waters. Although the interface is, highly hydrated, it supports tight binding and has a considerable degree, of specificity. The biological activity of scIFN-gamma confirms that the, scIFN-gamma:IFN-gammaRalpha complex represents a productive intermediate, and that it can effectively recruit the other required component, IFN-gammaRbeta, to signal based on the 1:1:1 complex.
Disease
Known diseases associated with this structure: AIDS, rapid progression to OMIM:[147570], Aplastic anemia OMIM:[147570], BCG infection, generalized familial OMIM:[107470], H. pylori infection, susceptibility to OMIM:[107470], Hepatitis C virus, resistance to OMIM:[147570], Interferon, immune, deficiency OMIM:[147570], Mycobacterial infection, atypical, familial disseminated OMIM:[107470], TSC2 angiomyolipomas, renal, modifier of OMIM:[147570], Tuberculosis, susceptibility to OMIM:[107470], Tuberculosis, susceptibility to OMIM:[147570]
About this Structure
1FYH is a Protein complex structure of sequences from Homo sapiens with CL as ligand. Full crystallographic information is available from OCA.
Reference
The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex., Randal M, Kossiakoff AA, Structure. 2001 Feb 7;9(2):155-63. PMID:11250200
Page seeded by OCA on Mon Nov 12 16:58:16 2007
