A molecular breadboard: Removal and replacement of subunits in a hepatitis B virus capsid

Lye Siang Lee, Nicholas Brunk, Daniel G. Haywood, David Keifer, Elizabeth Pierson, Panagiotis Kondylis, Joseph Che Yen Wang, Stephen C. Jacobson, Martin F. Jarrold, Adam Zlotnick

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Hepatitis B virus (HBV) core protein is a model system for studying assembly and disassembly of icosahedral structures. Controlling disassembly will allow re-engineering the 120 subunit HBV capsid, making it a molecular breadboard. We examined removal of subunits from partially crosslinked capsids to form stable incomplete particles. To characterize incomplete capsids, we used two single molecule techniques, resistive-pulse sensing and charge detection mass spectrometry. We expected to find a binomial distribution of capsid fragments. Instead, we found a preponderance of 3 MDa complexes (90 subunits) and no fragments smaller than 3 MDa. We also found 90-mers in the disassembly of uncrosslinked HBV capsids. 90-mers seem to be a common pause point in disassembly reactions. Partly explaining this result, graph theory simulations have showed a threshold for capsid stability between 80 and 90 subunits. To test a molecular breadboard concept, we showed that missing subunits could be refilled resulting in chimeric, 120 subunit particles. This result may be a means of assembling unique capsids with functional decorations.

Original languageEnglish (US)
Pages (from-to)2170-2180
Number of pages11
JournalProtein Science
Issue number11
StatePublished - Nov 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology


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