NSF Award
1817338
Multimeric ATPases drive the mechanics of biology, facilitating critical biosynthetic pathways and controlling cellular and viral dynamics. An exceptionally powerful multimeric ATPase is the terminase motor that pumps DNA into viral capsids during assembly of dsDNA viruses. These extremely powerful terminase enzymes provide unique opportunities for uncovering how the force of motor output is governed. Understanding of motor mechanism could lead to development of new nanomaterials that respond to the environment, or nanodevices for targeted delivery of nucleic acids. Furthermore, these motors are of interest in development of novel sequencing technologies using nanopores for reading out nucleic acid sequence. This innovative research and outreach platform will explore the terminase's nanotechnological potential, while also providing educational opportunities at the high school and graduate level.<br/><br/>The structural mechanism of terminase motors at the atomic level will be elucidated using a combination of x-ray crystallography, cryo-electron microscopy and molecular modelling to determine three-dimensional structures of terminases and their complexes. New structures will be used to generate hypotheses for motor mechanism, which will then be tested using innovative biochemical and biophysical assays. These studies will complement the investigators research on AAA+ ATPases to reveal how ATPases couple chemical energy to mechanical motion, providing broad and novel insights into the mechanisms, regulation, and evolution of molecular motors.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
