1H3U

CRYSTAL STRUCTURE OF THE HUMAN IGG1 FC-FRAGMENT,GLYCOFORM (M3N2F)2

Summary for 1H3U

• Entry DOI: 10.2210/pdb1h3u/pdb
• Related: 1AJ7 1D5B 1D5I 1D6V 1DN2 1E4K 1FC1 1FC2 1FCC 1H3U 1H3V 1H3W 1H3X 1H3Y 1HZH 1I7Z 1IIS 1IIX 2RCS
• Descriptor: IG GAMMA-1 CHAIN C REGION, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: immune system, fc-fragment, glycosylation, fcgr, antibody, effector functions
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 52367.01

Authors

Krapp, S.,Mimura, Y.,Jefferis, R.,Huber, R.,Sondermann, P. (deposition date: 2002-09-19, release date: 2003-01-23, Last modification date: 2024-11-13)

Primary citation

Krapp, S.,Mimura, Y.,Jefferis, R.,Huber, R.,Sondermann, P.
Structural Analysis of Human Igg-Fc Glycoforms Reveals a Correlation between Glycosylation and Structural Integrity.
J.Mol.Biol., 325:979-, 2003

PubMed Abstract: 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.

PubMed: 12527303
DOI: 10.1016/S0022-2836(02)01250-0

Experimental method

X-RAY DIFFRACTION (2.4 Å)