Research in Dr. Todd Yeates' laboratory addresses problems at the interface of molecular biology, mathematics and computation. Interests cover various aspects of protein structure and function, protein sequence and evolution and protein assembly and design. Yeates and his colleagues are using protein crystallography to explore the structure and function of enzymes whose activities are of special interest, such as adenylosuccinate (implicated in some forms of autism) and protein aspartyl methyltransferase (important in repairing damaged proteins). Computational approaches are being used to attack the long-standing phase problem of macromolecular crystallography, most recently by pattern recognition methods.
In the area of protein evolution, the researchers are taking advantage of the data from the growing number of organisms whose genomes have been completely sequenced to investigate unusual mechanisms of protein evolution, and to develop new approaches to the problem of predicting the cellular roles of proteins from their amino acid sequences. Finally, building on the lab's continuing interest in the symmetry of protein assemblies, the researchers have developed a new and general strategy for designing novel proteins that self-assemble into a variety of regular structures or material, including cages, filaments, layers and crystals. They call this new class of designed structures "nanohedra," to suggest their scale and symmetry.
Selected Cancer-Related Publications:
Yeates TO, Norcross TS, King NP. Knotted and topologically complex proteins as models for studying folding and stability. Curr Opin Chem Biol. 2007 Dec;11(6):595-603. Epub 2007 Nov 9.
Laidman J, Forse GJ, Yeates TO. Conformational change and assembly through edge beta strands in transthyretin and other amyloid proteins. Acc Chem Res. 2006 Sep;39(9):576-83.
Bowers PM, O'Connor BD, Cokus SJ, Sprinzak E, Yeates TO, Eisenberg D. Utilizing logical relationships in genomic data to decipher cellular processes. FEBS J. 2005 Oct;272(20):5110-8.
Kudryashov DS, Sawaya MR, Adisetiyo H, Norcross T, Hegyi G, Reisler E, Yeates TO. The crystal structure of a cross-linked actin dimer suggests a detailed molecular interface in F-actin. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13105-10. Epub 2005 Sep 1.
Bowers PM, Cokus SJ, Eisenberg D, Yeates TO. Use of logic relationships to decipher protein network organization. Science. 2004 Dec 24;306(5705):2246-9.