1jrh
COMPLEX (ANTIBODY/ANTIGEN)
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OverviewOverview
The extracellular interferon gamma receptor alpha-chain comprises two, immunoglobulin-like domains, each with fibronectin type-III topology, which are responsible for binding interferon gamma at the cell surface., The epitopes on the human receptor recognized by three neutralizing, antibodies, A6, gammaR38 and gammaR99, have been mapped by homolog, scanning mutagenesis. In this way, a loop connecting beta-strands C and C', in the N-terminal domain was identified as a key component of the epitopes, bound by A6 and gammaR38, whereas gammaR99 binds to the C-terminal domain, in a region including strands A and B and part of the large C'E loop. The, epitope for A6 was confirmed in a crystal structure of a complex between a, recombinant N-terminal receptor domain and the Fab fragment from A6, determined by X-ray diffraction to 2.8 A resolution. The antibody-antigen, interface buries 1662 A2 of protein surface, including 22 antibody, residues from five complementarity determining regions, primarily through, interactions with the CC' surface loop of the receptor. The floor of the, antigen binding cavity is formed mainly by residues from CDR L3 and CDR H3, while a surrounding ridge is formed by residues from all other CDRs except, L2. Many potential polar interactions, as well as 13 aromatic side-chains, four in VL, six in VH and three in the receptor, are situated at the, interface. The surface of the receptor contacted by A6 overlaps to a large, extent with that contacted by interferon-gamma, in the ligand-receptor, complex. However, the conformation of this epitope is very different in, the two complexes, demonstrating that conformational mobility in a surface, loop on this cytokine receptor permits steric and electrostatic, complementarity to two quite differently shaped binding sites.Copyright, 1997 Academic Press Limited
DiseaseDisease
Known diseases associated with this structure: BCG infection, generalized familial OMIM:[107470], H. pylori infection, susceptibility to OMIM:[107470], Mycobacterial infection, atypical, familial disseminated OMIM:[107470], Tuberculosis, susceptibility to OMIM:[107470]
About this StructureAbout this Structure
1JRH is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Neutralizing epitopes on the extracellular interferon gamma receptor (IFNgammaR) alpha-chain characterized by homolog scanning mutagenesis and X-ray crystal structure of the A6 fab-IFNgammaR1-108 complex., Sogabe S, Stuart F, Henke C, Bridges A, Williams G, Birch A, Winkler FK, Robinson JA, J Mol Biol. 1997 Nov 7;273(4):882-97. PMID:9367779
Page seeded by OCA on Mon Nov 12 17:43:45 2007