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) alpha and beta 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 P2(1)2(1)2(1), with cell dimensions a = 78.5 A, b = 85.5 A and c = 67.5 A. A data set to 2.0 resolution has been collected for these crystals. Tetragonal crystals, space group P4(1)2(1)2 (or P4(3)2(1)2), with unit cell dimensions a = 69.0 A and c = 185.5 A are obtained using methylpentanediol as precipitant at pH 8.5. Data to 2.8 A 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 beta. An accurate structure of the receptor and an understanding of its mechanism will provide a basis for rational drug design.
Rodseth
L E
LE
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas 75235-9050.
Brandhuber
B
B
Devine
T Q
TQ
Eck
M J
MJ
Hale
K
K
Naismith
J H
JH
Sprang
S R
SR
D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D008233:Lymphotoxin-alpha / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000652:urine; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008233:Lymphotoxin-alpha; D010446:Peptide Fragments; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha