1h3v
CRYSTAL STRUCTURE OF THE HUMAN IGG1 FC-FRAGMENT,GLYCOFORM (G2F)2,SG P212121
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OverviewOverview
Antibodies may be viewed as adaptor molecules that provide a link between, humoral and cellular defence mechanisms. Thus, when antigen-specific IgG, antibodies form antigen/antibody immune complexes the effectively, aggregated IgG can activate a wide range of effector systems. Multiple, effector mechanisms result from cellular activation mediated through a, family of IgG-Fc receptors differentially expressed on leucocytes. It is, established that glycosylation of IgG-Fc is essential for recognition and, activation of these ligands. IgG antibodies predominate in human serum and, most therapeutic antibodies are of the IgG class.The IgG-Fc is a homodimer, of N-linked glycopeptide chains comprised of two immunoglobulin domains, (Cgamma2, Cgamma3) that dimerise via inter-heavy chain disulphide bridges, at the N-terminal region and non-covalent interactions between the, C-terminal Cgamma3 domains. The overall shape of the IgG-Fc is similar to, that of a "horseshoe" with a majority of the internal space filled by the, oligosaccharide chains, only attached through asparagine residues 297.To, investigate the influence of individual sugar (monosaccharide) residues of, the oligosaccharide on the structure and function of IgG-Fc we have, compared the structure of "wild-type" glycosylated IgG1-Fc with that of, four glycoforms bearing consecutively truncated oligosaccharides. Removal, of terminal N-acetylglucosamine as well as mannose sugar residues resulted, in the largest conformational changes in both the oligosaccharide and in, the polypeptide loop containing the N-glycosylation site. The observed, conformational changes in the Cgamma2 domain affect the interface between, IgG-Fc fragments and FcgammaRs. Furthermore, we observed that the removal, of sugar residues permits the mutual approach of Cgamma2 domains resulting, in the generation of a "closed" conformation; in contrast to the "open", conformation which was observed for the fully galactosylated IgG-Fc, which, may be optimal for FcgammaR binding. These data provide a structural, rationale for the previously observed modulation of effector activities, reported for this series of proteins.
About this StructureAbout this Structure
1H3V is a Single protein structure of sequence from Homo sapiens. Structure known Active Site: 1. Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity., Krapp S, Mimura Y, Jefferis R, Huber R, Sondermann P, J Mol Biol. 2003 Jan 31;325(5):979-89. PMID:12527303
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