Two Crystal Forms of the Extracellular Domain of Type I Tumor Necrosis Factor Receptor

• Published in: Journal of molecular biology Vol. 239; no. 2; pp. 332 - 335
• Main Authors: Rodseth, Lynn E., Brandhuber, Barbara, Devine, Tracey Q., Eck, Michael J., Hale, Karin, Naismith, James H., Sprang, Stephen R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 03.06.1994; Elsevier
• Subjects: Binding Sites; Biological and medical sciences; Crystalline structure; crystallography; Crystallography, X-Ray - methods; drug design; Fundamental and applied biological sciences. Psychology; Humans; Lymphotoxin-alpha - metabolism; Molecular biophysics; Peptide Fragments - blood; Peptide Fragments - chemistry; Peptide Fragments - urine; receptors; Receptors, Tumor Necrosis Factor - chemistry; Structure in molecular biology; tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; crystallography; tumor necrosis factor; receptors; drug design; Human; Unit cell; Membrane receptor; Crystal form; Tumor necrosis factor; Crystallization; X ray diffraction; Extracellular; Molecular domain; Structural analysis
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1994.1371

The soluble extracellular domain of human type I tumor necrosis factor receptor (sTNFrI) is a 161 residue polypeptide found in scrum 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 P 212121, 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 P 41212 (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 pII) 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.