Stoichiometry of the interaction between the major histocompatibility complex-related Fc receptor and its Fc ligand.
The neonatal Fc receptor (FcRn) transports immunoglobulin G (IgG) across epithelia, providing passive immunity and protecting serum IgG from degradation. For both functions, FcRn binds to IgG at the acidic pH of intracellular vesicles (pH </= 6.5) and releases IgG at the basic pH of the bloodstream (pH approximately 7.4). Crystallographic studies show that rat FcRn can interact with the Fc portion of IgG in a repeating array in which FcRn dimers are bridged by Fc fragments to create an "oligomeric ribbon" with a 2n:n stoichiometry. The stoichiometry of the interaction between soluble FcRn and Fc has been reported as either 2:1 for rat FcRn [Huber et al. (1993) J. Mol. Biol. 230, 1077-1083] or 1:1 for mouse FcRn [Popov et al. (1996) Mol. Immunol. 33, 521-530]. To ascertain the reasons for this difference, we analyzed complexes formed in solution between soluble rat or mouse FcRn and Fc. Using a gel-filtration assay under nonequilibrium conditions, we find that both forms of FcRn produce 2:1 receptor-ligand complexes, but that alterations of the carbohydrate moieties on mouse FcRn can result in an apparent stoichiometry of 1:1. However, under equilibrium conditions, all forms of FcRn make complexes with a 2:1 stoichiometry. We conclude that rat and mouse FcRn share the same general ligand binding properties but that small differences in affinities can produce apparent differences under nonequilibrium conditions.
Sánchez
L M
LM
Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
Penny
D M
DM
Bjorkman
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002850:Chromatography, Gel; D006224:Cricetinae; D005110:Extracellular Space / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008285:Major Histocompatibility Complex; D008358:Mannose / Q000378:metabolism; D051379:Mice; D051381:Rats; D011961:Receptors, Fc / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D012995:Solubility
D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D011961:Receptors, Fc; D008358:Mannose