|Title||Quantifying the energetics of cooperativity in a ternary protein complex.|
|Publication Type||Journal Article|
|Year of Publication||2002|
|Authors||Andersen, PS, Schuck, P, Sundberg, EJ, Geisler, C, Karjalainen, K, Mariuzza, RA|
|Date Published||2002 Apr 23|
|Keywords||Animals, Binding Sites, Enterotoxins, HLA-DR1 Antigen, Humans, Kinetics, Ligands, Macromolecular Substances, Mice, Models, Chemical, Models, Molecular, Multiprotein Complexes, Protein Binding, Proteins, Receptors, Antigen, T-Cell, alpha-beta, Staphylococcus aureus, Temperature, Thermodynamics|
The formation of complexes involving more than two proteins is critical for many cellular processes, including signal transduction, transcriptional control, and cytoskeleton remodeling. Energetically, these interactions cannot always be described simply by the additive effects of the individual binary reactions that make up the overall complex. This is due, in large part, to cooperative interactions between separate protein domains. Thus, a full understanding of multiprotein complexes requires the quantitative analysis of cooperativity. We have used surface plasmon resonance techniques and mathematical modeling to describe the energetics of cooperativity in a trimolecular protein complex. As a model system for quantifying cooperativity, we studied the ternary complex formed by the simultaneous interaction of a superantigen with major histocompatibility complex and T cell receptor, for which a structural model is available. This system exhibits positive and negative cooperativity, as well as augmentation of the temperature dependence of binding kinetics upon the cooperative interaction of individual protein components in the complex. Our experimental and theoretical analysis may be applicable to other systems involving cooperativity.