During viral infection many viruses use a conserved motor mechanism to package double-stranded DNA (dsDNA) into the viral capsid. These DNA packaging motors are required for infectivity, and operate as several individual subunits working together as a motor. The packaging motor of lambda bacteriophage will be studied using biochemical and biophysical techniques (SA I), characterizing packaging deficient mutant subunits of the packaging motor, and (SA 11), mixing mutant and wild-type subunits to form chimeric packaging motors, and characterizing DNA packing. Understanding the exact deficiencies in motor subunits, and how one to several subunits can "poison" a motor will provide insight into the way these subunits work together and communicate to the other parts of the motor. Knowledge of this communication improves our general understanding of viruses and viral infection and will characterize an ideal viral process that can be disrupted to abolish or limit viral infection. Relevance: Understanding the mechanism of DNA packaging in viruses will identify further drug targets which can be used in therapy in viruses such as the clinically relevant herpes groups. Furthermore, the understanding of DNA packaging motors, among the most powerful of the characterized biological motors, has direct applications in molecular motors as nanomachines.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM090565-03
Application #
8209074
Study Section
Special Emphasis Panel (ZRG1-F08-F (20))
Program Officer
Flicker, Paula F
Project Start
2010-01-01
Project End
2012-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
3
Fiscal Year
2012
Total Cost
$53,942
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Andrews, Benjamin T; Catalano, Carlos Enrique (2013) Strong subunit coordination drives a powerful viral DNA packaging motor. Proc Natl Acad Sci U S A 110:5909-14
Medina, Eva Margarita; Andrews, Benjamin T; Nakatani, Eri et al. (2011) The bacteriophage lambda gpNu3 scaffolding protein is an intrinsically disordered and biologically functional procapsid assembly catalyst. J Mol Biol 412:723-36
Tsay, James M; Sippy, Jean; DelToro, Damian et al. (2010) Mutations altering a structurally conserved loop-helix-loop region of a viral packaging motor change DNA translocation velocity and processivity. J Biol Chem 285:24282-9