Robert J. Fletterick
University of California, San Francisco
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Primary Section: 29, Biophysics and Computational Biology Secondary Section: 21, Biochemistry Membership Type:
Emeritus
(elected 2010)
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Research Interests
The methods of structural biology have triggered my investigations into learning the functional mechanisms of enzymes, scaffolding proteins and molecular motors. We have learned the atomic level controls that glycogen phosphorylases need to fragment glycogen in different tissues and how the regulatory mechanisms evolved from yeast to mammals. The precise roles of constellations of amino acids in forming specific interactions with substrates and for speeding peptide hydrolysis was revealed for proteases through protein engineering and biochemistry. Analysis of the structures of five kinesins in varied conformations and with a protein regulator showed how ATP hydrolysis and mechanical motion by a motor protein are intertwined to power motility in cells. Some of the mysteries of clathrin, an assembly vehicle for some membrane vesicles, were revealed by high resolution X-ray analysis and biochemistry. Nuclear receptors form the core of many transcription machines. Our studies showed how hormone binding triggers the assembly of the machine and taught us the importance of specific matching of hormone to receptor. The subjects or our studies have varied widely, but the questions have been fundamental and the answers satisfying and sometimes surprising. We uncovered many beautiful designs in biology that verify structure is function and function is structure.
