Thursday, 9 May 2019

The rules behind virus scaffold construction


A team of researchers including Northwestern Engineering faculty has expanded the understanding of how virus shells self-assemble, an important step toward developing techniques that use viruses as vehicles to deliver targeted drugs and therapeutics throughout the body.

By performing multiple amino acid substitutions, the researchers discovered instances of epistasis, a phenomenon in which two changes produce a behavior different from the behavior that each change causes individually.

"We found occurrences where two separate single amino acid changes caused the virus shell to break or become really unstable, but making both changes together produced a stable structure that functioned better than ever," said Danielle Tullman-Ercek, associate professor of chemical and biological engineering at the McCormick School of Engineering.

The latest research builds on the team's progress by using SyMAPS to analyze multiple amino acid changes within the MS2 particle, a requirement to effectively manipulate virus shells in the future, Tullman-Ercek said. Researchers studied every double amino acid combination along a polypeptide loop located within the MS2 scaffold and measured how the virus scaffold was affected.

One factor producing epistasis was balancing the amino acid charges that were substituted, said Tullman-Ercek, a member of Northwestern's Center for Synthetic Biology. Swapping two positively charged amino acids, for instance, caused the particle to repel and break apart, but balancing a single positive amino acid change with a separate negative charge compensated the switch and preserved stability.

See:

Emily C. Hartman, Marco J. Lobba, Andrew H. Favor, Stephanie A. Robinson, Matthew B. Francis, Danielle Tullman-Ercek. Experimental Evaluation of Coevolution in a Self-Assembling Particle. Biochemistry, 2018; 58 (11): 1527 DOI: 10.1021/acs.biochem.8b00948

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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