1ncf
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(New page: 200px<br /> <applet load="1ncf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ncf, resolution 2.25Å" /> '''A NEW PARADIGM FOR ...)
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Revision as of 16:13, 12 November 2007
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A NEW PARADIGM FOR TUMOR NECROSIS FACTOR SIGNALLING
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Periodic fever, familial OMIM:[191190]
About this Structure
1NCF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystallographic evidence for dimerization of unliganded tumor necrosis factor receptor., Naismith JH, Devine TQ, Brandhuber BJ, Sprang SR, J Biol Chem. 1995 Jun 2;270(22):13303-7. PMID:7768931
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