Project Summary

My partner Marilena LoVerde and I work under the supervision of Dr. Aina Cohen and Dr. Paul Ellis of the Protein Crystallography Department at the Stanford Synchrotron Radiation Laboratory (SSRL). Our project for this summer has several components. We will grow hen egg white lysozyme and recombinant sperm whale myoglobin protein crystals under known conditions for the department’s staff use as calibration standards. We will attempt to find ideal conditions in which to grow gamma-aminobutyric acid (GABA) receptor protein crystals. We will also develop a comprehensive, instructional web page for using the software and hardware at the SSRL beam lines with relevant background information and experiment setup, data collection and analysis guidelines.
 

 At SSRL, electrons travelling at high speeds in the electron storage ring emit radiation when their path is bent by a magnetic field. The X-rays from this radiation are stored and used at the SSRL beam lines. Since X-ray’s wavelength is on the order of magnitude of atomic structure, these X-rays are used to produce a diffraction pattern for any molecule in crystalline form. This diffraction pattern is then used to discern the molecule’s structure. Crystalline form is necessary to produce an interpretable diffraction pattern.
 

Proteins, however, do not naturally form crystals. They are highly sensitive to the conditions in which other molecules are usually crystallized; certain temperatures, pH levels or solution makeup destroys the protein molecules. Therefore, a major feat in crystallography is to find the conditions necessary for a protein to grow into crystalline form. Mari and I will try to do this for the GABA receptor. Since GABA is a major inhibitory neurotransmitter in all animals, if we find the right conditions for GABA receptor crystal growth, then Dr. Cohen and Dr. Ellis can use the crystals for diffraction experiments that will lead to the discovery of the receptor’s structure. Knowing GABA receptor’s structure means that drugs can be developed for inhibiting or enhancing GABA’s actions in the brain. This has enormous medical significance for all diseases related to GABA.