Dynamics of Protein-Pheromone Interactions:Temperature Dependent Spectral Density Mapping and Molecular Dynamics Simulations.
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Proceedings |
| Conference | Magnetic Resonance in Physics, Chemistry, Biology, and Medicine |
| MU Faculty or unit | |
| Citation | |
| Field | Biochemistry |
| Keywords | NMR; relaxation; spectral density; dynamics; MUP-I; pheromone interactions |
| Description | Binding of mouse pheromones to major urinary proteins (MUPs) represents a typical example of interactions between lipocalins and their small hydrophobic ligands. Previously, we observed that the backbone flexibility of MUP-I increased slightly upon pheromone binding, in contrast to the decreased flexibility expected for induced-fit interactions. To shed the light on this unusual observation, we have performed an independent study adopting different methodology. Backbone dynamics of mouse major urinary protein I (MUP-I) was studied by 15N NMR relaxation at multiple temperatures for a complex of MUP-I with its natural pheromonal ligand, 2-sec-4,5-dihydrothiazole, and for the free protein. Graphical analysis of the reduced spectral density values provided an unbiased qualitative picture of the internal motions. Quantitative parameters were obtained using a novel method of simultaneous data fitting at multiple temperatures to several models of different complexity. The relaxation data were complemented by the molecular dynamics simulations. Comparison of the experimental and simulated order parameters and the information about slow conformational exchanges provided a picture of the molecular motions and offered an explanation for the observed difference in the dynamics of the free and bound MUP-I. |
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