Characterization of the 2:1 complex between the class I MHC-related Fc receptor and its Fc ligand in solution.
The neonatal Fc receptor (FcRn) facilitates the transfer of maternal immunoglobulin G (IgG) to offspring and prolongs the half-life of serum IgG. FcRn binds IgG in acidic intracellular vesicles and releases IgG upon exposure to the basic pH of the bloodstream. The crystal structure of an FcRn/Fc complex revealed FcRn dimers bridged by homodimeric Fc molecules to create an oligomeric array with two receptors per Fc [Burmeister et al. (1994) Nature 372, 379-383], consistent with the 2:1 FcRn:Fc stoichiometry observed in solution [Huber et al. (1993) J. Mol. Biol. 230, 1077-1083; Sánchez et al. (1999) Biochemistry 38, 9471-9476]. Two distinct 2:1 FcRn/Fc complexes were present in the cocrystal structure: a complex containing an FcRn dimer interacting with an Fc and a complex in which single FcRn molecules are bound to both sides of the Fc homodimer. To determine which of the two possible 2:1 FcRn/Fc complexes exists in solution, we generated recombinant Fc molecules with zero, one, and two FcRn binding sites and studied their interactions with a soluble form of rat FcRn. The wild-type Fc with two FcRn binding sites binds two FcRn molecules under all assay conditions, and the nonbinding Fc with no FcRn binding sites shows no specific binding. The heterodimeric Fc with one FcRn binding site binds one FcRn molecule, suggesting that the 2:1 FcRn/wild-type Fc complex formed in solution consists of single FcRn molecules binding to both sides of Fc rather than an FcRn dimer binding to a single site on Fc.
Martin
W L
WL
Division of Biology 156-29 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
Bjorkman
P J
PJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D051381:Rats; D011961:Receptors, Fc / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D020349:Surface Plasmon Resonance
D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D011961:Receptors, Fc; D011994:Recombinant Proteins; D012996:Solutions