Biography
Carlos Bustamante received a B.S. degree from Cayetano Heredia University in Lima, Peru, a masters in biochemistry from San Marcos University, and a Ph.D. in biophysics in 1981 from the University of California, Berkeley. Since 1994, Dr. Bustamante has held an appointment as a Howard Hughes Medical Institute Investigator. In 1998, he became the director for the Advance Microscopies Department at Lawrence Berkeley National Laboratory, and a Professor of Physics, Professor of Chemistry, as well as of Molecular and Cell Biology at Berkeley. His research interests include single molecule manipulation methods and their application to investigate various biochemical processes: torque measurements on single DNA molecules, reversible folding of single RNA and protein molecules by force, and the mechanochemistry of nucleic-acid binding molecular motors. He was nominated as America's Best in Time magazine (2001), received the Biological Physics Prize of the American Physical Society (2002), and he accepted the Alexander Hollaender Award in Biophysics from the National Academy of Science (2004). He has also received the Hans Neurath Prize of the Protein Society (2004), the Richtmyer Memorial Lecture Award by the American Association of Physics Teachers (2005), and a Honorary Doctorate (Honoris Causa) by the University of Chicago (2005).
Dr. Bustamante has given well over 400 presentations and lectures and has published over 200 papers in several journals such at PNAS, Nature, Science, and Cell. He currently serves as a member of the Science Advisory Board of the Searle Scholars Program. He is a member of the National Academy of Sciences. He has served in the Science Advisory Committee of the Burroughs-Wellcome Fund , and currently serves in the Board of Directors of the BWF. He also holds several other advisory roles within the University of California, Berkeley and the larger scientific community.
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Grabbing the Cat by the Tail:
Following the Packaging of DNA Inside the Capsid of Bacteriophage phi 29 One Molecule at a Time and at Base-Pair Resolution
Abstract:
I will present our recent results on the packaging of DNA by the connector motor at the base of the head of bacteriophage f 29. As part of their infection cycle, many viruses must package their newly replicated genomes inside a protein capsid to insure its proper transport and delivery to other host cells. Bacteriophage f 29 packages its 6.6 mm long double-stranded DNA into a 42 nm dia. x 54 nm high capsid via a portal complex that possesses 5 ATPases that hydrolyze ATP. This process is remarkable because entropic, electrostatic, and bending energies of the DNA must be overcome to package the DNA to near-crystalline density. We have used optical tweezers to pull on single DNA molecules as they are packaged, thus demonstrating that the portal complex is a force generating motor. We find that this motor can work against loads of up to ~57 picoNewtons on average, making it one of the strongest molecular motors ever reported. Movements of over 5 mm are observed, indicating high processivity. Pauses and slips also occur, particularly at higher forces. We establish the force-velocity relationship of the motor and find that the rate-limiting step of the motor's cycle is force dependent even at low loads. Interestingly, the packaging rate decreases as the prohead is filled, indicating that an internal pressure builds up due to DNA compression. We estimate that at the end of the packaging the capsid pressure is ~6 MegaPascals, corresponding to an internal force of ~52 pN acting on the motor. The biological implications of this internal pressure and the mechano-chemical efficiency of the engine are discussed. We have also investigated the coordination between the mechanical and the chemical steps in the operation of the motor and have been able to propose the first putative cycle for this molecular machine. We determine, within this cycle, the step at which the chemical energy is converted into mechanical work and we have characterized the nature of the interactions between the motor and the DNA. Finally, high resolution optical tweezers experiments are also making it possible for us to investigate in detail the operation of this motor and the coordination among the ATPases during the overall motor cycle.
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