Search

The X-ray crystal structure of the complex of the extracellular domain of the human 55 kd tumor necrosis factor (TNF) receptor with human TNF beta has been determined at 2.85 A resolution. The complex has three receptor molecules bound symmetrically to one TNF beta trimer. The receptor fragment, a very elongated end to end assembly of four similar folding domains, binds in the groove between two adjacent TNF beta subunits. The structure of the complex defines the orientation of the ligand with respect to the cell membrane and provides a model for TNF receptor activation. The novel fold of the TNF receptor structure is likely to be representative of the nerve growth factor (NGF)/TNF receptor family as a whole.

We show that a protein of 63 amino acids is the product of the rop gene, a gene which negatively regulates the copy number of plasmids of the ColE1 family. Rop protein purified to homogeneity inhibits ColE1 plasmid replication in a bacterial extract. Furthermore, we show that Rop inhibition requires RNA I. In a purified in vitro system that can support primer transcription and processing, Rop affects primer formation in two ways: first, it elicits transcription termination oat nucleotide 220, and second, it increases the ability of RNA I to inhibit RNAase H processing of the primer. The analysis of these data and the comparison with the results obtained in vivo with transcription fusion experiments allow us to propose a tentative model of the molecular mechanism underlying Rop-RNA I inhibition.