5UUI

Crystal Structure of Spin-Labeled T77C TNFa

Summary for 5UUI

• Entry DOI: 10.2210/pdb5uui/pdb
• Descriptor: Tumor necrosis factor, S-[(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioate (3 entities in total)
• Functional Keywords: t77c, tnfa, tnf alpha, cytokine, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Single-pass type II membrane protein . Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein. Tumor necrosis factor, soluble form: Secreted. C-domain 1: Secreted. C-domain 2: Secreted: P01375
• Total number of polymer chains: 1
• Total formula weight: 17724.16

Authors

Horanyi, P.S.,Dranow, D.M.,Ceska, T. (deposition date: 2017-02-16, release date: 2017-08-02, Last modification date: 2024-10-16)

Primary citation

Carrington, B.,Myers, W.K.,Horanyi, P.,Calmiano, M.,Lawson, A.D.G.
Natural Conformational Sampling of Human TNF alpha Visualized by Double Electron-Electron Resonance.
Biophys. J., 113:371-380, 2017

PubMed Abstract: Double electron-electron resonance in conjunction with site-directed spin labeling has been used to probe natural conformational sampling of the human tumor necrosis factor α trimer. We suggest a previously unreported, predeoligomerization conformation of the trimer that has been shown to be sampled at low frequency. A model of this trimeric state has been constructed based on crystal structures using the double-electron-electron-resonance distances. The model shows one of the protomers to be rotated and tilted outward at the tip end, leading to a breaking of the trimerous symmetry and distortion at a receptor-binding interface. The new structure offers opportunities to modulate the biological activity of tumor necrosis factor α through stabilization of the distorted trimer with small molecules.

PubMed: 28746848
DOI: 10.1016/j.bpj.2017.06.007

Experimental method

X-RAY DIFFRACTION (1.4 Å)