1tnf

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spinqualitylabelsall models 1tnf, resolution 2.6Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Asthma, susceptibility to OMIM:[191160], Dementia, vascular, susceptibility to OMIM:[191160], Malaria, cerebral, susceptibility to OMIM:[191160], Migraine without aura, susceptibility to OMIM:[191160], Septic shock, susceptibility to OMIM:[191160]

About this Structure

1TNF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding., Eck MJ, Sprang SR, J Biol Chem. 1989 Oct 15;264(29):17595-605. PMID:2551905

Page seeded by OCA on Mon Nov 12 19:26:11 2007