The proposed studies will elucidate the molecular mechanisms of transmembrane signaling by membrane receptors and membrane fusion during neurotransmission by using the recently advanced technique of dipolar spin labeling. In the dipolar spin labeling technique, the distance in the range of 7-25 A between two site-specific spin labels is determined. Data analysis and computer modeling on a sufficiently large set of these distances will give a three dimensional model of the protein structure at backbone resolution, as well as protein dynamics. Applications of this technique will be focused on the bacterial aspartate chemotaxis receptor (AR), a helical transmembrane receptor which plays a pivotal role in the input state of signal transduction, and the synaptic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex, which plays a central role in the docking and fusion of synaptic vesicles to the plasma membrane.
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