Protein Structure/Function Relationships and Structural Genomics
With the availability of complete genomes, protein structure elucidation becomes increasingly important as a tool for predicting protein function. Nuclear magnetic resonance, NMR, provides a powerful solution technique for structure determination. Development of new NMR strategies for determining protein structure are necessary to minimize the time required to calculate a protein global fold and increase the effectiveness of NMR in global fold identification. Specifically, we are developing paramagnetic techniques that utilize both distance and angular restraints for rapid protein global fold elucidation. These techniques should be particularly applicable to larger molecular mass proteins and complexes. Currently, we are developing and utilizing this methodology on human leptin and several RNA-binding proteins (the ribonuclease barnase and it�s intracellular inhibitor barstar, helicases, and aminoacyl �tRNA synthetases).

Specific interactions between proteins form the basis of many essential biological processes. Contraction in cardiac muscle is regulated through calcium �dependent protein-protein interactions that modulate the activity of actomyosin ATPase. Key to transmission of the calcium signal, which controls the actomyosin ATPase is the interaction between troponins C, I, and T in the troponin complex. The project aims at obtaining a molecular understanding of calcium activation and hormonal modulation of the cardiac troponin complex. Knowledge of the molecular mechanisms of activation and modulation of cardiac muscle contraction should permit the design of new strategies for altering cardiac muscle contraction in disease states. Our research utilizes a synergistic blend of molecular biology and structural methods to study structure/function relationships in cardiac muscle. Our primary structural technique is NMR, but we are also using a variety of biophysical techniques including X-ray scattering, neutron diffraction, and calorimetry.

Support for trainees is available from a Training Grant in Cardiovascular Research. This training program can be viewed at the following web site: CV Training Grant