 |
|
Title
|
|
The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution.
|
|
|
Authors
|
|
M.J.Eck,
M.Ultsch,
E.Rinderknecht,
A.M.de Vos,
S.R.Sprang.
|
|
|
Ref.
|
|
J Biol Chem, 1992,
267,
2119-2122.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The three-dimensional structure of recombinant human lymphotoxin (residues
24-171 of the mature protein) has been determined by x-ray crystallography at
1.9-A resolution (Rcryst = 0.215 for I greater than 3 sigma (I)). Phases were
derived by molecular replacement using tumor necrosis factor (TNF-alpha) as a
search model. Like TNF-alpha, lymphotoxin (LT) folds to form a "jellyroll"
beta-sheet sandwich. Three-fold related LT subunits form a trimer stabilized
primarily by hydrophobic interactions. A cluster of 6 basic residues around the
3-fold axis may account for the acid lability of the trimer. Although the
structural cores of TNF-alpha and LT are similar, insertions and deletions
relative to TNF-alpha occur in loops at the "top" of the LT trimer and
significantly alter the local structure and the overall shape trimer is highly
conserved. The sites of two mutations (Asp-50 and Tyr-108) that abolish the
cytotoxicity of LT are contained within poorly ordered loops of polypeptide
chain that flank the cleft between neighboring subunits at the base of the
molecule, suggesting that the receptor recognizes an intersubunit binding site.
|
|
|
|