Structurally adaptive hot spots at a protein interaction interface on TRAF3

Publisher Website
Google Scholar
Abstract
Tumor necrosis factor (TNF) signaling is controlled by receptors and intracellular signaling pathways that activate the NF‐κB transcription factor. The resulting signals elicit immune responses and have important implications for disorders such as autoimmunity or allergic reactions. TNF‐receptor‐associated factors (TRAFs) bind to the cytoplasmic portion of TNFRs as well as downstream regulators and thus are co‐inducers of the signal transduction. TRAF3 binds to diverse receptors and regulators by accomodating a conserved motif that is embedded in completely different structural frameworks. Thus, the protein–protein contact region on TRAF3 represents a binding interface that is structurally and functionally adaptive. In this report, three ‘hot spots’ at the TRAF3 protein–interaction interface are defined that provide the principal contact regions for different binding partners. The side‐chains of residues at these ‘hot spots’ are flexible and undergo movements on binding the different partners. These side chain rearrangements provide a structural adaptability that promotes interaction with a variety of distinct proteins. It is proposed that similar adaptive ‘hot spots’ are also present on the binding surfaces of TRAF1, TRAF2 and TRAF5. Copyright © 2002 John Wiley & Sons, Ltd.