Human FcγRI (GST-Fusion)

ABB’s FcγRI-glutathione-S-transferase (GST) fusion protein (P7131D) was produced in human embryonic kidney cells (HEK-293T), affinity purified through the glutathione-4B column and formulated to phosphate buffered saline by size exclusion chromatography. GST portion of the fusion protein enables the dimeric formation of the P7131D. The non-denaturing purification process circumvents the denaturation/renaturation conditions associated with other affinity processes as such the native folding of the FcγRI remains undisturbed.

Read all details below including Quick Specs.

** Please note: For orders over 1 mg, please inquire here

Quick Spec

Description

Human FcγRI, a 374 amino acid protein, binds human IgG1, IgG3 and IgG4 but not to IgG2. Human FcγRI is constitutively expressed on monocytes, macrophages, and dendritic cells, and can be induced to express on neutrophils and mast cells. The extracellular domain of human FcγRI contains three Ig-like domains as compared with all other canonical Fcγ receptors each of which contains only two Ig-like extracellular domains. This unique membrane-proximal third Ig-like domain is responsible for its higher affinity to IgG. Mutations of IgG1 in the lower hinge region to IgG2 equivalent, namely, P233P, L235A, and G236D, lead to loss of binding. In addition, FcγRI exhibits a reduced binding to IgG4, and the F234 (Leu in IgG1) and S331 (Pro in IgG1) are implicated. Furthermore, an IgG3 with a partially deleted hinge region exhibits a reduced binding as well. Thus, on IgG, the FcγRI binding region extended from the hinge to the CH2-CH3 interface. The N-linked glycan associated with the Asn297 located at the CH2-CH3 interface is particularly critical for binding of IgG to FcγRI.  Similar to other canonical Fcγ receptors, FcγRI binds to human IgG1 at a 1:1 stoichiometry.  FcγRI associated with the FcR common g chain homodimer, possibly through the interaction of His in FcγRI and Asp of the g chain in their respective transmembrane regions. Ligation of FcγRI results in increase of the Hck and Lyn kinases activity. Two other FcγRI genes (FcγRIB and FcγRIC) have been described. While neither have been identified at the protein level, transfection of the FcγRIB cDNA in COS cells showed binding of aggregated, but no monomeric, IgG and that individuals that are homozygous of a non-sense mutation of the FcγRIA gene are apparently healthy, suggesting the FcγRIB can be functional.

Amino Acid Sequence

References

1. Holtrop T, Budding K, Brandsma AM, Leusen JHW. Targeting the high affinity receptor, FcγRI, in autoimmune disease, neuropathy, and cancer. Immunother Adv. 2022;2(1):ltac011. Epub 20220528. doi: 10.1093/immadv/ltac011. PubMed PMID: 36284837; PubMed Central PMCID: PMC9585681.
   
2. Alemán OR, Rosales C. Human neutrophil Fc gamma receptors: different buttons for different responses. J Leukoc Biol. 2023;114(6):571-84. doi: 10.1093/jleuko/qiad080. PubMed PMID: 37437115.
   
3. FcγRs Across Species. B Moldt and AJ Hessell, Chapter 8, Antibody Fc, Elsevier Inc., p.145-157, 2014
4. IgG subclasses and allotypes: from structure to effector functions. G Vidarsson, G Dekkers, and T Rispens, Frontiers in Immunol. 5:1-17, 2014.
5. Functional and clinical consequences of Fc receptor polymorphic and copy number variants. S Bournazos, JM Woof, SP Hart, and I Dransfield. Clin and Exp Immunol. 157: 244-254, 2009
6. Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high affinity IgG binding. J Lu, J chu, Z Zou, NB Hamacher, MW Rixon, and PD Sun. PNAS 112:833-838, 2015