title: The structure of human lymphotoxin (tumor necrosis factor-beta) at 1.9-A resolution.
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.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9050.
authors.forename: M J
authors.initials: MJ
authors.lastname: Eck
authors.forename: M
authors.initials: M
authors.lastname: Ultsch
authors.forename: E
authors.initials: E
authors.lastname: Rinderknecht
authors.forename: A M
authors.initials: AM
authors.lastname: de Vos
authors.forename: S R
authors.initials: SR
authors.lastname: Sprang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha