title: High-resolution mass spectrometry of viral assemblies: molecular composition and stability of dimorphic hepatitis B virus capsids.
abstract: Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fundamental. HBV capsids are unusual in that they exhibit two distinct icosahedral geometries, nominally composed of 90 and 120 dimers with masses of approximately 3 and approximately 4 MDa, respectively. Here, a mass spectrometric approach was used to determine the masses of both capsids to within 0.1%. It follows that both lattices are complete, consisting of exactly 180 and 240 subunits. Nanoindentation experiments by atomic-force microscopy indicate that both capsids have similar stabilities. The data yielded a Young's modulus of approximately 0.4 GPa. This experimental approach, anchored on very precise and accurate mass measurements, appears to hold considerable potential for elucidating the assembly of viruses and other macromolecular particles.
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Uetrecht
authors.forename: Cees
authors.initials: C
authors.lastname: Versluis
authors.forename: Norman R
authors.initials: NR
authors.lastname: Watts
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Roos
authors.forename: Gijs J L
authors.initials: GJ
authors.lastname: Wuite
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wingfield
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
mesh_terms: D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D006515:Hepatitis B virus / Q000737:chemistry* / Q000648:ultrastructure; D013058:Mass Spectrometry; D018625:Microscopy, Atomic Force; D013816:Thermodynamics; D019065:Virus Assembly