04/18/18 -4:00 PM to 5:00 PM
Kolthoff Lectureship #1: Professor Carlos J. Bustamante
Izaak M. Kolthoff Lectureship in Chemistry
"Use of Crooks' Theorem to Study the Interdomain Folding Cooperativity of a Protein"
A reception for Professor Bustamante follows this seminar in the Kate and Michael Bárány Conference Room (117/119) Smith Hall.
The three-dimensional structures of proteins often show a modular architecture comprised of discrete structural regions or domains. Cooperative communications between these regions is important to catalysis, regulation and efficient folding; lack of coupling has been implicated in the formation of fibrils and other misfiling pathologies. How different structural regions of a protein communicate and contribute to a protein's overall energetics and folding; however, is still poorly understood. Here, we use a single-molecule optical tweezers approach to indue the selective unfolding of particular regions of T4 lysozyme and monitor the effect of other regions not directly acted on by force. We investigate how the topological organization of a proven (the order of structural elements along the sequence) affects the coupling and folding cooperatively between its domains. To probe the status of the regions not directly subjected to force, we determine the free energy changes during mechanical unfolding using Crooks' fluctuation theorem. We pull on topological variants (circular per mutants) and find that the topological organization of the polypeptide chain critically determine the folding cooperativity between domains and thus what parts of the folding/unfolding landscape are explored. We speculate that proteins may have evolved to select certain topologies that increase coupling between regions to avoid areas of the landscape that lead to kinetic trapping and misfolding.
Professor Bustamante is a professor of chemistry, physics, and molecular and cell biology, and the Raymond and Beverly Sackler Professor in Biophysics at the University of California, where he has been a faculty member and researcher since 1998. He received his bachelor’s degree from the Universidad Peruana Cayetano Heredia in Lima, Peru, his master's degree in biochemistry from the Universidad Nacional Mayor de San Marcos in Lima, and his doctorate in biophysics from University of California, Berkeley, where he studied with Ignacio Tinoco Jr. As a post-doctoral fellow at the Lawrence Berkeley National Laboratory, Bustamante studied with Marcos Maestre. Before moving to Berkeley, he was a professor at the University of Mexico, and professor of chemistry and member of the Insitute of Molecular Biology at the University of Oregon. He also was a Howard Hughes Medical Institute investigator. He is a Fellow of the American Physical Society, Fellow of the National Academy of Sciences, and Howard Hughes Medical Institute Investigator.
Professor Bustamante’s laboratory specializes in single molecule biophysics, where his researchers can track and measure the activity of individual enzymes. By looking at each enzyme, they can parse out effects which are not resolvable in bulk experiments. The researchers use optical tweezers, magnetic tweezers, atomic force microscopy, single molecule fluorescence, fluorescence correlation spectroscopy, and super-resolution photo-activatable light microscopy (PALM). They are interested in studying how the cell converts chemical energy into mechanical work through highly specialized molecular machines. The generation, transduction, and regulation of force are key to many central processes in the cell. Many enzymes, such as polymerases, are motors which move along a cellular track, using chemical energy to take regulated steps and control synthesis. These techniques are used to understand:
- DNA packaging into bacteriophage Φ29 capsids;
- translation and protein folding;
- protein degradation by ClpXP;
- PALM-mitochondrial fission, and
- catalysis-enhanced enzyme diffusion
His group is affiliated with the departments of Molecular and Cell Biology, Physics, and Chemistry as well as the Physical Biosciences Division at the Lawrence Berkeley National Laboratory.
Kolthoff Lectureship in Chemistry
Izaak Maurits Kolthoff was born on February 11, 1894, in Almelo, Holland. He died on March 4, 1993, in St. Paul, Minnesota. In 1911, he entered the University of Utrecht, Holland. He published his first paper on acid titrations in 1915. On the basis of his world-renowned reputation, he was invited to join the faculty of the University of Minnesota’s Department of Chemistry in 1927. By the time of his retirement from the University in 1962, he had published approximately 800 papers. He continued to publish approximately 150 more papers until his health failed. His research, covering approximately a dozen areas of chemistry, was recognized by many medals and memberships in learned societies throughout the world, including the National Academy of Sciences and the Nichols Medal of the American Chemical Society. Best known to the general public is his work on synthetic rubber. During World War II, the government established a comprehensive research program at major industrial companies and several universities, including Minnesota. Kolthoff quickly assembled a large research group and made major contributions to the program. Many of Kolthoff’s graduate students went on to successful careers in industry and academic life and, in turn, trained many more. In 1982, it was estimated that approximately 1,100 Ph.D. holders could trace their scientific roots to Kolthoff. When the American Chemical Society inaugurated an award for excellence in 1983, he was the first recipient.