Virus assembly occurs following a pH- or Ca2+-triggered switch in the thermodynamic attraction between structural protein capsomeres

Chuan, Yap P., Fan, Yuan Y., Lua, Linda H.L. and Middelberg, Anton P.J. (2010) Virus assembly occurs following a pH- or Ca2+-triggered switch in the thermodynamic attraction between structural protein capsomeres. Journal of The Royal Society Interface, 7 44: 409-421. doi:10.1098/rsif.2009.0175

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Author Chuan, Yap P.
Fan, Yuan Y.
Lua, Linda H.L.
Middelberg, Anton P.J.
Title Virus assembly occurs following a pH- or Ca2+-triggered switch in the thermodynamic attraction between structural protein capsomeres
Journal name Journal of The Royal Society Interface   Check publisher's open access policy
ISSN 1742-5689
Publication date 2010-03-06
Year available 2009
Sub-type Article (original research)
DOI 10.1098/rsif.2009.0175
Volume 7
Issue 44
Start page 409
End page 421
Total pages 13
Place of publication United Kingdom
Publisher The Royal Society Publishing
Collection year 2011
Language eng
Subject C1
Formatted abstract
Viral self-assembly is of tremendous virological and biomedical importance. Although theoretical and crystallographic considerations suggest that controlled conformational change is a fundamental regulatory mechanism in viral assembly, direct proof that switching alters the thermodynamic attraction of self-assembling components has not been provided. Using the VP1 protein of polyomavirus, we report a new method to quantitatively measure molecular interactions under conditions of rapid protein self-assembly. We show, for the first time, that triggering virus capsid assembly through biologically relevant changes in Ca2+ concentration, or pH, is associated with a dramatic increase in the strength of protein molecular attraction as quantified by the second virial coefficient (B-22). B-22 decreases from -2.3 x 10(-4) mol ml g(-2) (weak protein-protein attraction) to -2.4 x 10(-3) mol ml g(-2) (strong protein attraction) for metastable and Ca2+-triggered self-assembling capsomeres, respectively. An assembly-deficient mutant (VP1C Delta 63) is conversely characterized by weak protein-protein repulsion independently of chemical change sufficient to cause VP1 assembly. Concomitant switching of both VP1 assembly and thermodynamic attraction was also achieved by in vitro changes in ammonium sulphate concentration, consistent with protein salting-out behaviour. The methods and findings reported here provide new insight into viral assembly, potentially facilitating the development of new antivirals and vaccines, and will open the way to a more fundamental physico-chemical description of complex protein self-assembly systems. © 2009 The Royal Society.
Keyword Virus
Cooperative
Self-assembly
Conformation
Second virial coefficient
Field-Flow Fractionation
Self-interaction chromatography
Tobacco Mosaic-virus
Size-exclusion Chromatography
Liquid Phase-separation
Murine-polyoma-virus
Light-scattering
Conformational-change
Aqueous-solution
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 07 Feb 2010, 10:05:05 EST