Membrane-anchored human FcRn can oligomerize in the absence of IgG.
FcRn is unique among immunoglobulin G (IgG) Fc receptors in that it is structurally closely related to major histocompatibility complex class I molecules and likewise consists of an alpha-chain and beta2-microglobulin. Crystallographic data show that rat FcRn alpha-chain/beta2m heterodimers can further dimerize via ionic interactions and a carbohydrate handshake. Intriguingly, however, no dimers are found in crystals of human FcRn, probably because the charged amino acids and the carbohydrate implicated in dimerization of rat FcRn are not conserved. Here, we show that although a secreted soluble form of human FcRn does not dimerize, the membrane-anchored receptor can form both non-covalent and covalent dimers. Furthermore, dimerization of human FcRn occurs in the absence of its ligand, IgG.
Praetor
Asja
A
Institute of Molecular and Cell Biology, Epithelial Cell Biology Laboratory, 30 Medical Drive, Singapore, Singapore.
Jones
Robert M
RM
Wong
Woei Ling
WL
Hunziker
Walter
W
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D011233:Precipitin Tests; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011961:Receptors, Fc / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012995:Solubility
D004220:Disulfides; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C100688:Fc receptor, neonatal