453796 A Single Amino Acid Change Confers a Radical Change in the Structure of a Virus-like Particle

Monday, November 14, 2016: 8:00 AM
Continental 8 (Hilton San Francisco Union Square)
Emily Hartman1, Michael Asensio2, Norma Morella3, Jeff Glasgow4, Christopher Jakobson5, Banumathi Sankaran6, Peter H. Zwart6 and Danielle Tullman-Ercek5, (1)Chemistry, UC Berkeley, Berkeley, CA, (2)Department of Bioengineering, UC Berkeley - UCSF, Berkeley, CA, (3)Department of Plant and Microbial Biology, UC Berkeley, Berkeley, CA, (4)Chemistry, University of California, Berkeley, Berkeley, CA, (5)Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, (6)Lawrence Berkeley National Lab, Berkeley, CA

Single amino acid mutations can alter secondary and tertiary structure in proteins, but mutations that alter quaternary structure are less well documented. Here, we use MS2 bacteriophage as a model for quaternary structure, and we show that a single amino acid mutation can shrink the global virus-like particle (VLP) from 27nm to 18nm in diameter. Crystallizing this unique VLP mutant revealed a uniform, stable shift from a T=3 to a T=1 icosahedral viral capsid. These small VLPs maintain the ability to disassemble and reassemble in vitro and can attach to the F pili of E. coli—which is required for infectivity. Furthermore, these mutant VLPs can be chemically modified to load cargo such as drugs or fluorophores. We are currently designing new strategies to systematically introduce single amino acid mutations into the VLP and screen for altered quaternary structure. Altogether, these structurally-distinct VLPs have implications for de novo prediction of quaternary structure, drug delivery, and viral evolution.

Extended Abstract: File Not Uploaded
See more of this Session: Biomolecular Engineering
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division