1NCF

A NEW PARADIGM FOR TUMOR NECROSIS FACTOR SIGNALLING

Summary for 1NCF

• Entry DOI: 10.2210/pdb1ncf/pdb
• Descriptor: TUMOR NECROSIS FACTOR RECEPTOR (2 entities in total)
• Functional Keywords: binding protein, cytokine, signalling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein: P19438
• Total number of polymer chains: 2
• Total formula weight: 36671.66

Authors

Naismith, J.H.,Sprang, S.R. (deposition date: 1994-10-12, release date: 1995-12-07, Last modification date: 2024-10-30)

Primary citation

Naismith, J.H.,Devine, T.Q.,Brandhuber, B.J.,Sprang, S.R.
Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor.
J.Biol.Chem., 270:13303-13307, 1995

PubMed Abstract: Activation of the cell surface receptors for tumor necrosis factor (TNF) is effected by the aggregation of cytoplasmic domains that occurs when the extracellular domains of two or three receptors bind to trimeric TNF alpha or TNF beta. The structure of the type I TNF receptor extracellular domain (sTNF-R1), crystallized in the absence of TNF, has now been determined at 2.25-A resolution. The receptor itself is an elongated molecule comprising four disulfide-rich domains in a nearly linear array. Contrary to expectations, the unliganded domains are found to associate into dimers of two distinct types, in which monomers are related by local two-fold axes of symmetry. In one case, the receptors are antiparallel to each other and associate through an interface that overlaps the TNF binding site. If intact receptors were capable of such an association, their cytoplasmic domains would be separated by over 100 A. This interaction could inhibit signaling in the absence of TNF. Parallel dimers are also observed in which the dimer interface is well separated from the TNF binding site. Associations among TNF-bound parallel dimers could cause receptor clustering. Both dimers bury substantial areas of protein surface and are formed by polar and non-polar interactions.

PubMed: 7768931
DOI: 10.1074/jbc.270.22.13303

Experimental method

X-RAY DIFFRACTION (2.25 Å)