Abstract
Human FcalphaRI (CD89) is the receptor specific for IgA, an immunoglobulin that is abundant in mucosa and is also found in high concentrations in serum. Although FcalphaRI is an immunoglobulin Fc receptor (FcR), it differs in many ways from FcRs for other immunoglobulin classes. The genes of most FcRs are located on chromosome 1 at 1q21-23, whereas FcalphaRI is on chromosome 19, at 19q13.4, a region called the leukocyte receptor complex, because it is clustered with several leukocyte receptor families including killer cell inhibitory receptors (KIRs) and leukocyte Ig-like receptors (LIRs). The amino acid sequence of FcalphaRI shares only 20% homology with other FcRs but it has around 35% homology with its neighboring LIRs and KIRs. In this work, we analyzed the crystal structure of the ectodomain of FcalphaRI and examined structure similarities between FcalphaRI and KIR2DL1, KIR2DL2 and LIR-1. Our data show that FcalphaRI, KIRs, and LIRs share a common hydrophobic core in their interdomain interface, and FcalphaRI is evolutionally closer to LIR than KIR.
Highlights
Body-dependent cell cytotoxicity, oxidative bursts, and release of inflammatory mediators [1]
Fc␣RI belongs to the immunoglobulin superfamily and contains an extracellular region of 206 amino acids, a transmembrane domain of 19 amino acids and a cytoplasmic region of 41 amino acids [4]
Fc␣RI is an immunoglobulin Fc receptor (FcR),1 it differs in many ways with FcRs for other immunoglobulin classes
Summary
Protein Expression and Purification—The construction and expression of the extracellular ligand binding domain of a human Fc␣RI will be described in detail elsewhere. Briefly, residues 1–207 of the mature sequence were subcloned into a Novagen pET-28a vector using the NcoI and XhoI restriction sites and an E. coli BL21(DE3) strain. Crystal Structure of the Ectodomain of Human Fc␣RI inclusion bodies were dissolved in a buffer containing 6 M guanidine hydrochloride and 5 mM dithiothreitol, and incubated for 2 h to unfold completely the misfolded protein of inclusion bodies. Crystallization, Data Collection, and Structure Determination—The Fc␣RI crystals were obtained by the hanging-drop method. The crystals were grown from a buffer of 11.4% polyethylene glycol-8000 in 100 mM sodium Hepes buffer, pH 7.6, containing 8% (v/v) ethanol glycol, 3% (v/v) Me2SO, and 50 mM MgCl2 as an additive, and protein concentration of ϳ12 mg/ml. The initial chain tracing and all subsequent model building were done using the program O [22], version 8.0. The model was initially refined as a rigid body with data 8.0 – 4.0 Å resolution. The final model contained 191 residues of Fc␣RI and 68 solvent molecules. Buried surface areas were calculated using SURFACE [35] with a 1.4-Å probe radius
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