Giant Protein Assemblies in Nature and by Design

McDonnell Douglas Engineering Auditorium

Professor Todd O. Yeates

Department of Chemistry and Biochemistry



Nature is replete with self-assembling molecular structures having diverse cellular functions.  The largest and most sophisticated types are built from many copies of one protein molecule (or a few distinct protein molecules) arranged following principles of symmetry.  Viral capsids are well-studied examples.  A number of equally sophisticated natural protein assemblies are only beginning to be appreciated.  Among them is a broad class of giant, capsid-like assemblies referred to as bacterial microcompartments.  They serve as primitive metabolic organelles in many bacteria by encapsulating sequentially acting enzymes within a selectively permeable protein shell.  Our laboratory has elucidated key mechanisms of these protein-based bacterial organelles through structural studies. Beyond their biological importance, complex protein assemblies like these have for many years represented an ultimate goal in protein design.  By exploiting principles of symmetry that are shared by nearly all natural self-assembling structures, we have developed methods for engineering novel proteins that assemble to form a variety of complex, symmetric architectures, including cages, extended two-dimensional layers, and three-dimensional crystalline materials.  The success of these strategies has been proven by designing and determining crystal structures of several giant, self-assembling protein cages (100-220 Å in diameter).  The ability to create sophisticated supramolecular structures from designed protein subunits opens the way to broad applications in synthetic biology.  Design principles and strategies will be discussed, along with current successes.


Bio: Yeates earned his Bachelor's degree at UCLA in 1983. He stayed on at UCLA and earned his PhD in 1988 while doing research under the direction of Prof. Douglas Rees. There he helped determine the crystal structure of the bacterial photosynthetic reaction center as part of a team racing to determine the first crystal structures of membrane proteins. He then moved to The Scripps Research Institute to do his postdoctoral research on the structure of poliovirus with Prof. James Hogle. Yeates returned to UCLA in 1990 to join the Faculty in the Department of Chemistry and Biochemistry. His interdisciplinary research, combining molecular biology with computing and mathematics, has focused on macromolecular structure and computational genomics. His varied research findings include: an explanation for why proteins crystallize in certain favored arrangements; the development of new equations for detecting disorder in x-ray diffraction data from protein crystals; the discovery of thermophilic microbes rich in intracellular disulfide bonds; development of comparative genomics methods; development of designed protein cages or 'nanohedra'; the discovery of novel topological features such as links and slipknots that stabilize thermostable proteins; and elucidation of the structure of the carboxysome shell and the shells of other bacterial microcompartments, which serves as primitive metabolic organelles inside many bacterial cells. Yeates is a member of the Molecular Biology Institute, the California Nanosystems Institute, the UCLA-DOE Institute of Genomics and Proteomics, and a Fellow of the American Association for the Advancement of Science. He has published approximately 150 research papers.