FcRn

Introduction

FcRn, also known as the neonatal Fc receptor or the Brambell receptor, is classified as a non-classical Fc gamma receptor (FcγR) as at the time of its discovery it was structurally unique and not thought to be involved in the immune response. Unlike classical FcγRs, FcRn is a beta-2-microglobulin (β2M) associated protein. It is structurally related to the major histocompatibility class I (MHC-I) family but is unable to present peptides to T cells.

FcRn is expressed in most cell types and is predominantly intracellular. In addition to binding IgG it also binds to albumin. These two proteins owe their long half-life to this interaction. FcRn is also responsible for the transport of IgG from mother to offspring, providing the naïve and immature immune system of the child with the experience and protection developed by the mother. The functions of FcRn are determined by whether IgG is a single monomeric molecule or an immune complex. As an immune complex FcRn has been shown to regulate the immune response as well as processing and presentation of antigens within the immune complex. Although FcRn is typically considered as the transport molecule, additional roles beyond this are still being elucidated.

Co-crystal structure (PDB: 4N0U) of FcRn in complex with an IgG Fc domain and human serum albumin. The FcRn heterodimer is shown in green (FCGRT) and grey (B2M). One half of the IgG Fc domain is shown in blue with albumin shown in pink, cyan and gold for domains I, II and III.

Product list

Filters

Species
Conjugate
Cat No. Species Product Description Host Sequence Tag Conjugate Purity & Activity Data Size & Price
HUFCRN-B Human Biotinylated human FcRn (FCGRT-B2M) heterodimer protein HEK293 A24-S297 & I21-M119 AVI & His Biotinylated
  • SDS-PAGE
  • SEC-HPLC
  • SPR
HUFCRN-U Human Human FcRn (FCGRT-B2M) heterodimer protein HEK293 A24-S297 & I21-M119 AVI & His Unconjugated
  • SDS-PAGE
  • SEC-HPLC
  • SPR

8 reasons to use Gamma Proteins

  • Purity - Final product purity is determined by SEC-HPLC with a quality threshold >95% monomer purity.

  • Activity - Biological activity of recombinant proteins is confirmed by Surface Plasmon Resonance.

  • Mammalian expression - All recombinant proteins are produced in Human Embryonic Kidney 293 (HEK293) cells, ensuring correct folding and post-translational modification.

  • Animal free - All proteins are manufactured in an animal component free platform with no carrier proteins added to the final products.

  • Reproducibility - All proteins are produced recombinantly and quality & activity is confirmed for every batch.

  • Low endotoxin - All products are prepared in an endotoxin free process to ensure they have < 1 EU / mg.

  • Site-specific biotinylation - All products contain an AVI-tag for site-specific biotinylation ensuring greater reproducibility and preferential orientation for assays.

  • Lyophilized - All products come lyophilized for longer stability and reduced environmental impact from transport.

Background

The neonatal Fc receptor (FcRn) is an approximately 45 kDa transmembrane glycoprotein with structural homology to MHC class I proteins. It is widely expressed in endothelial and epithelial cells and plays an important role in IgG homeostasis and antigen presentation by dendritic cells. FcRn is a heterodimer composed of a heavy chain, known as p51 or FCGRT, and a light chain, known as p14 or beta-2-microglobulin (β2M). FcRn has non-overlapping binding sites for the IgG Fc domain and albumin, which both mind to FcRn at mildly acidic pH (approximately pH 6.0) but not at neutral pH (approximately pH 7.4). FcRn cycles between the plasma membrane and acidified intracellular compartments of endothelial cells. It binds endocytosed IgG and albumin in the low pH vesicles and transports them to the plasma membrane for extracellular release at higher pH, as shown in the image below. This protects IgG and albumin from lysosomal degradation and helps maintain the circulating levels of both proteins.

For further information on the structure and functions of FcRn please see our FcRn resource page.

FcRn mediated recycling of IgG and albumin. In the early endosome IgG and/or albumin interacts with FcRn at pH 6.0. The FcRn complex is then recycled back to the cell surface and IgG and albumin are released at neutral pH thus rescuing them from lysosomal degradation.