Solution structure of human interleukin‐1 receptor antagonist protein

Abstract

Interleukin-1 receptor antagonist protein (IRAP) is a naturally occurring inhibitor of the interleukin-1 receptor. In contrast to IL-lb, IRAP binds to the IL-l receptor but does not elicit a physiological response. We have determined the solution structure of IRAP using NMR spectroscopy. While the overall topology of the two 153-residue proteins is quite similar, functionally critical differences exist concerning the residues of the linear amino acid sequence that constitute structurally homologous regions in the two proteins. Structurally homologous residues important for IL-l receptor binding are conserved between IRAP and IL-l/!?. By contrast, structurally homologous residues critical for receptor activation are not conserved between the two proteins.

Conformation and Side Chains Environments of Recombinant Human Interleukin-1 Receptor Antagonist (rh-IL-1ra) Probed by Raman, Raman Optical Activity, and UV-Resonance Raman Spectroscopy

“…These ROA features represent the typical β‐barrel super‐secondary structure 21. These results on rh‐IL‐1ra solution conformation from Raman and ROA are consistent with those obtained from multinuclear NMR spectroscopy of solution conformation and X‐ray diffraction of crystals 4–7…”

“…The rh‐IL‐1ra protein has 153 amino acid residues with a molecular weight of 17.25 kDa. The solution and crystal structures of rh‐IL‐1ra have been determined by multinuclear solution NMR4, 5 and X‐ray crystallography 6, 7. The rh‐IL‐1ra protein contains predominantly β‐sheet secondary structure that is composed of three β‐trefoils; each β‐trefoil consists of four β‐strands.…”

Head to Head Comparison of the Formulation and Stability of Concentrated Solutions of HESylated versus PEGylated Anakinra

“…As a result, daily administration of 100 mg protein as subcutaneous injection in the form of a highly concentrated solution (150 mg/mL) is required. Additionally, the protein is well studied with many literature reports about its biophysical properties and formulation, thus serving as a useful model protein. There are a few literature reports on the PEGylation of anakinra to increase its circulation time and reduce the dosing frequency .…”

Biophysical Characterization of Structural Properties and Folding of Interleukin-1 Receptor Antagonist

“…The amino acid sequence of IL-1ra is 26% identical to that of IL-1β 29 and its 3D structure has been determined by X-ray crystallography and NMR. [30][31][32][33] The high-resolution crystal structure of recombinant human IL-1ra is shown in Figure 1 (PDB ID: 1ILR 32 ). Although the crystal form of the protein is an asymmetric dimer, IL-1ra is monomeric in solution, including the experimental conditions of this study.…”