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Title
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Two crystal forms of the extracellular domain of type I tumor necrosis factor receptor.
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Authors
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L.E.Rodseth,
B.Brandhuber,
T.Q.Devine,
M.J.Eck,
K.Hale,
J.H.Naismith,
S.R.Sprang.
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Ref.
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J Mol Biol, 1994,
239,
332-335.
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PubMed id
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Abstract
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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.
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