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.
Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA.
L M
LM
Sánchez
D M
DM
Penny
P J
PJ
Bjorkman
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