1TNF

THE STRUCTURE OF TUMOR NECROSIS FACTOR-ALPHA AT 2.6 ANGSTROMS RESOLUTION. IMPLICATIONS FOR RECEPTOR BINDING

1TNF の概要

• エントリーDOI: 10.2210/pdb1tnf/pdb
• 分子名称: TUMOR NECROSIS FACTOR-ALPHA (1 entity in total)
• 機能のキーワード: lymphokine
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted: P01375
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 52106.19

構造登録者

Eck, M.J.,Sprang, S.R. (登録日: 1989-08-25, 公開日: 1990-01-15, 最終更新日: 2024-11-20)

主引用文献

Eck, M.J.,Sprang, S.R.
The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding.
J.Biol.Chem., 264:17595-17605, 1989

PubMed Abstract: The three-dimensional structure of tumor necrosis factor (TNF-alpha), a protein hormone secreted by macrophages, has been determined at 2.6 A resolution by x-ray crystallography. Phases were determined by multiple isomorphous replacement using data collected from five heavy atom derivatives. The multiple isomorphous replacement phases were further improved by real space symmetry averaging, exploiting the noncrystallographic 3-fold symmetry of the TNF-alpha trimer. An atomic model corresponding to the known amino acid sequence of TNF-alpha was readily built into the electron density map calculated with these improved phases. The 17,350-dalton monomer forms an elongated, antiparallel beta-pleated sheet sandwich with a "jelly-roll" topology. Three monomers associate intimately about a 3-fold axis of symmetry to form a compact bell-shaped trimer. Examination of the model and comparison to known protein structures reveals striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus. Locations of residues conserved between TNF-alpha and lymphotoxin (TNF-beta, a related cytokine known to bind to the same receptors as TNF-alpha) suggest that lymphotoxin, like TNF-alpha, binds to the receptor as a trimer and that the general site of interaction with the receptor is at the "base" of the trimer.

PubMed: 2551905

実験手法

X-RAY DIFFRACTION (2.6 Å)