Two crystal forms of the extracellular domain of type I tumor necrosis factor receptor

The soluble extracellular domain of human type I tumor necrosis factor receptor (sTNFrI) is a 161 residue polypeptide found in serum and urine. This domain tightly binds tumor necrosis factors (TNF) α and β and, as part of the whole receptor, initiates the powerful biological effects of TNF. The extracellular domain, typical of other TNF receptor superfamily members, comprises four cysteine-rich motifs. We have obtained two crystal forms of the sTNFrI. One crystal form is grown at pH 3.7 with MgSO₄ as the precipitant. These crystals are orthorhombic, space group P2₁2₁2₁, with cell dimensions a = 78.5 Å, b = 85.5 Å and c = 67.5 Å. A data set to 2.0 resolution has been collected for these crystals. Tetragonal crystals, space group P4₁2₁2 (or P4₃2₁2), with unit cell dimensions a = 69.0 Å and c = 185.5 Å are obtained using methylpentanediol as precipitant at pH 8.5. Data to 2.8 Å have been measured from these crystals. It appears that both unit cells may contain two molecules in the asymmetric unit. These crystal structures of sTNFrI may reveal possible conformational differences between receptor localized on the cell surface (high pH), the receptor in the endosomal compartments (low pH) and the receptor in a complex with tumor necrosis factor β. An accurate structure of the receptor and an understanding of its mechanism will provide a basis for rational drug design.