The Yeates laboratory is located at UCLA in the Department of Chemistry and Biochemistry. Our research covers the areas of molecular, structural and computational biology.
In the area of structural biology, our emphasis is on supra-molecular protein assemblies. Much of our recent work has focused on bacterial microcompartments -- extraordinary protein assemblies comprised of thousands of subunits reminiscent of viral capsids. They encapsulate a series of enzymes within a protein shell, which controls the transport of substrates and products into and out of the microcompartment interior. They serve as primitive metabolic organelles in many bacteria. Our structural studies on these systems provided the first three-dimensional views of the shell proteins, and have generated long-needed mechanistic hypotheses for how bacterial microcompartments function.
In our synthetic-biology work, we are focusing on synthetically designed protein assemblies as vehicles for understanding the evolution of natural assemblies and as potentially valuable materials for nanotechnology applications. We have developed general strategies for designing proteins that self-assemble into large, highly regular architectures such as molecular cages and extended two and three-dimensional arrays. The successful results of a number of very recent experiments emphasize the exciting long-term potential of these strategies in the nanotechnology field.
In our computational genomics work, we have focused on methods for detecting patterns across whole genomic sequence databases in order to infer protein function and to learn new cell biology. These 'non-homology' or 'genomic context' methods have provided a new paradigm for exploiting genomic data. In a specific application of computational and structural genomics to archaeal microbes, we have shown that in a major branch of the Archaeal kingdom, thermophilic microbes use disulfide bonding as a key mechanism for protein stability; this unexpected finding challenges the textbook view regarding the rarity of disulfide bonds in cytosolic environments.
In the area of protein crystallography, we are pursuing problems of both theoretical and practical interest. This includes the introduction of new equations for analyzing X-ray diffraction data for various forms of disorder. Our theoretical work has also addressed, and largely answered, the long-standing puzzle of why proteins crystallize preferentially in only a few strongly favored space group symmetries, out of 65 possibilities. That analysis led to the prediction that proteins would crystallize with much greater ease if they could be prepared synthetically in racemic form (i.e. as a mixture of the biological enantiomer and its mirror image synthesized from D-amino acids). We continue to promote this as a future avenue for overcoming the problem of crystallizing macromolecules. In a separate line of attack, we have developed other strategies for crystallization based on a combination of protein engineering and chemical or metal-based 'synthetic symmetrization'.