Detection of late intermediates in virus capsid assembly by charge detection mass spectrometry

Elizabeth E. Pierson, David Z. Keifer, Lisa Selzer, Lye Siang Lee, Nathan C. Contino, Joseph C.Y. Wang, Adam Zlotnick, Martin F. Jarrold

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The assembly of hundreds of identical proteins into an icosahedral virus capsid is a remarkable feat of molecular engineering. How this occurs is poorly understood. Key intermediates have been anticipated at the end of the assembly reaction, but it has not been possible to detect them. In this work we have used charge detection mass spectrometry to identify trapped intermediates from late in the assembly of the hepatitis B virus T = 4 capsid, a complex of 120 protein dimers. Prominent intermediates are found with 104/105, 110/111, and 117/118 dimers. Cryo-EM observations indicate the intermediates are incomplete capsids and, hence, on the assembly pathway. On the basis of their stability and kinetic accessibility we have proposed plausible structures. The prominent trapped intermediate with 104 dimers is attributed to an icosahedron missing two neighboring facets, the 111-dimer species is assigned to an icosahedron missing a single facet, and the intermediate with 117 dimers is assigned to a capsid missing a ring of three dimers in the center of a facet.

Original languageEnglish (US)
Pages (from-to)3536-3541
Number of pages6
JournalJournal of the American Chemical Society
Volume136
Issue number9
DOIs
StatePublished - Mar 5 2014

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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