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PMID: 21258385 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interrogating viral capsid assembly with ion mobility-mass spectrometry.

Nature chemistry ·Vol. 3 ·No. 2 ·2011-02-00 ·Pages 126-32

Uetrecht C, Barbu IM, Shoemaker GK, van Duijn E, Heck AJ

Abstract

Most proteins fulfil their function as part of large protein complexes. Surprisingly, little is known about the pathways and regulation of protein assembly. Several viral coat proteins can spontaneously assemble into capsids in vitro with morphologies identical to the native virion and thus resemble ideal model systems for studying protein complex formation. Even for these systems, the mechanism for self-assembly is still poorly understood, although it is generally thought that smaller oligomeric structures form key intermediates. This assembly nucleus and larger viral assembly intermediates are typically low abundant and difficult to monitor. Here, we characterised small oligomers of Hepatitis B virus (HBV) and norovirus under equilibrium conditions using native ion mobility mass spectrometry. This data in conjunction with computational modelling enabled us to elucidate structural features of these oligomers. Instead of more globular shapes, the intermediates exhibit sheet-like structures suggesting that they are assembly competent. We propose pathways for the formation of both capsids.

MeSH Terms
Capsid/chemistry,metabolism Capsid Proteins/chemistry,metabolism Hepatitis B virus/chemistry,metabolism Humans Mass Spectrometry/methods Models, Molecular Norovirus/chemistry,metabolism Protein Conformation Virus Assembly
Chemicals
Capsid Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Uetrecht Charlotte
Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
Barbu Ioana M
Shoemaker Glen K
van Duijn Esther
Heck Albert J R
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Article Info
Journal
Nature chemistry
Abbr.
Nat Chem
ISSN
1755-4349
DOI
10.1038/nchem.947
Published
2011-02-00
Epub
2010-00-19
Pages
126-32
Language
English
Region
England
NLM ID
101499734
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1038/nchem.947 View journal details
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