Discovery of a Third Type of Biomotor

The third type of biomotors using the revolution mechanism without rotation was discovered in 2013, and subsequently found widespread in bacteria, animal viruses, bacteriophages, and is expected to be prevalent in eukaryotic cells. DNA translocation motors are ubiquitous in living systems for mitosis, chromosome segregation, bacterial binary fission, viral genomic trafficking, RNA transcription, nuclear pore transport, viral genome packaging and DNA replication/ repair/homologous recombination/Holliday junction resolution. The motion events are accomplished by biomotors using ATP as energy. Biomotors were once classified into two categories: linear and rotation motors. For decades, dsDNA packaging motors of viruses have been popularly believed to be a five-fold rotation motor. However, extensive studies revealed that none of the motor components rotate during DNA packaging. The puzzle concerning how the spiral-shape motor nut can drive the helical dsDNA bolt without rotation of either the bolt or the nut has been solved by the finding of revolution mechanism without rotation. By analogy, rotation resembles the Earth rotating on its own axis for one cycle every 24 hours, while revolution resembles the Earth revolving around the Sun, one circle per 365 days (see animations: http://nanobio.uky.edu/movie.html). Revolution motors can be distinguished from rotation motors by channel size and chirality: left-handed channel wall for revolution motors in an anti-chiral arrangement with DNA; and right-handed for rotation motors as parallel threads with DNA. Larger channel (>3 nm) for revolution motors to revolve the 2-nm dsDNA inside the channel, and smaller channel (2 nm) for rotation motors to maintain close contact between the channel wall and dsDNA. The direction of motion is controlled by channel chirality and rectification. Binding of ATP to the ATPase results in entropy change of the ATPase, leading to a high affinity for dsDNA. ATP hydrolysis results in a second entropy change with a low DNA-affinity, resulting in the release of dsDNA for concomitant transfer to the adjacent subunit regulated by inter-subunit interaction. Coordination of several vector factors in the same direction make the motor unusually powerful and effective. Revolution mechanism that avoids DNA coiling and tangling for translocating the lengthy genomic could save much bioenergy. The application of the motor components for single pore sensing, single molecular finger printing, potential high throughput dsDNA sequencing, earlier disease single antibody or antigen detection, the methods for the development of highly potent drugs base on motor mechanisms, and how the studies on the motor pRNA of bacteriophage phi29 DNA packaging motor leads to the emergence of the field of RNA nanotechnology will be presented.

About the speaker

Ph.D from U Minnesota; postdoc NIH; Purdue assistant Prof 1990; tenured 1993; full Prof 1997, Biomed Engineering Endowed Chair U Cincinnati 2007; Endowed Chair of Nanobiotech U Kentucky 2012; Director NIH NDC 2006-2011; current U Kentucky Director of Nanobiotech Center; Director of NCI CNPP: RNA Nanotech for Cancer Therapy. Constructed the first viral DNA packaging motor (PNAS 1986), discovered phi29 motor pRNA (Science 1987); discovered pRNA hexamer (Mol Cell 1998), pioneered RNA nanotechnology (Mol Cell 1998, featured in Cell 1998; Nature Nanotech 2010, 2011); built a system to detect single-fluorophores (EMBOJ 2007); incorporated phi29 motor channel into membrane (Nature Nanotech 2009) for single pore sensing and DNA sequencing; discovered a third class of biomotor using revolution mechanism; developed approaches for ultra-potent drugs; received Pfizer Distinguished Faculty Award; Purdue Faculty Scholar Award; Lions Club Cancer Res Award; Distinguished Alumni of U Minnesota; 100 Years Distinguished Chinese Alumni of U Minnesota; editorial board of 7 nanotech journals; reported numerous times by TV such as ABC, NBC, BBC; featured by NIH, NSF, MSNBC, NCI and ScienceNow; member of two prominent national nanotech initiatives by NSF and NIH; NIH/NCI Intramural Site-visit Review Panel twice; Examination Panel of Chinese National Academy of Sciences since 2014.