An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles

Richard McGonigle, Wei Boon Yap, Swee Tin Ong, Derek Gatherer, Saskia E. Bakker, Wen Siang Tan, David Bhella

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Virus-like particles composed of the core antigen of hepatitis B virus (HBcAg) have been shown to be an effective platform for the display of foreign epitopes in vaccine development. Heterologous sequences have been successfully inserted at both amino and carboxy termini as well as internally at the major immunodominant epitope. We used cryogenic electron microscopy (CryoEM) and three-dimensional image reconstruction to investigate the structure of VLPs assembled from an N-terminal extended HBcAg that contained a polyhistidine tag. The insert was seen to form a trimeric spike on the capsid surface that was poorly resolved, most likely owing to it being flexible. We hypothesise that the capacity of N-terminal inserts to form trimers may have application in the development of multivalent vaccines to trimeric antigens. Our analysis also highlights the value of tools for local resolution assessment in studies of partially disordered macromolecular assemblies by cryoEM.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalJournal of Structural Biology
Volume189
Issue number2
DOIs
Publication statusPublished - 1 Feb 2015

Fingerprint

Viral Core Proteins
Hepatitis B Core Antigens
Hepatitis B virus
Virion
Vaccines
Antigens
Immunodominant Epitopes
Computer-Assisted Image Processing
Three-Dimensional Imaging
Capsid
Epitopes
Electron Microscopy
polyhistidine

Keywords

  • Cryo-electron microscopy
  • Hepatitis B virus
  • Local resolution
  • Three-dimensional reconstruction
  • Vaccine
  • Virus-like particle

ASJC Scopus subject areas

  • Structural Biology

Cite this

An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles. / McGonigle, Richard; Yap, Wei Boon; Ong, Swee Tin; Gatherer, Derek; Bakker, Saskia E.; Tan, Wen Siang; Bhella, David.

In: Journal of Structural Biology, Vol. 189, No. 2, 01.02.2015, p. 73-80.

Research output: Contribution to journalArticle

McGonigle, Richard ; Yap, Wei Boon ; Ong, Swee Tin ; Gatherer, Derek ; Bakker, Saskia E. ; Tan, Wen Siang ; Bhella, David. / An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles. In: Journal of Structural Biology. 2015 ; Vol. 189, No. 2. pp. 73-80.
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