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PubMed · 12447905

Structurally adaptive hot spots at a protein interaction interface on TRAF3.

Kathryn R Ely·Chenglong Li
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Abstract

Tumor necrosis factor (TNF) signaling is controlled by receptors and intracellular signaling pathways that activate the NF-kappaB 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.

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Amino AcidsAnimalsBinding SitesHumansHydrophobic and Hydrophilic InteractionsIn Vitro TechniquesModels, MolecularMolecular StructureProtein Structure, QuaternaryProtein SubunitsProteinsReceptors, Tumor Necrosis FactorSignal TransductionStatic ElectricityTNF Receptor-Associated Factor 3Journal ArticleReview

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Kathryn R Ely, Chenglong Li. Structurally adaptive hot spots at a protein interaction interface on TRAF3.. https://doi.org/10.1002/jmr.589

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