Albumin binding to FcRn: distinct from the FcRn-IgG interaction.
The MHC-related Fc receptor for IgG (FcRn) protects albumin and IgG from degradation by binding both proteins with high affinity at low pH in the acid endosome and diverting both from a lysosomal pathway, returning them to the extracellular compartment. Immunoblotting and surface plasmon resonance studies show that both IgG and albumin bind noncooperatively to distinct sites on FcRn, that the affinity of FcRn for albumin decreases approximately 200-fold from acidic to neutral pH, and that the FcRn-albumin interaction shows rapid association and dissociation kinetics. Isothermal titration calorimetry shows that albumin binds FcRn with a 1:1 stoichiometry and the interaction has hydrophobic features as evidenced by a large positive change in entropy upon binding. Our results suggest that the FcRn-albumin interaction has unique features distinct from FcRn-IgG binding despite the overall similarity in the pH-dependent binding mechanism by which both ligands are protected from degradation.
Chaudhury
Chaity
C
Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Brooks
Charles L
CL
Carter
Daniel C
DC
Robinson
John M
JM
Anderson
Clark L
CL
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal