Manipulation of the mechanical properties of a virus by protein engineering

*Departamento de Física de la Materia Condensada C-III and
^†Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

Edited by Alan R. Fersht, University of Cambridge, Cambridge, United Kingdom, and approved January 5, 2008 (received for review August 24, 2007)

Abstract

In a previous study, we showed that the DNA molecule within a spherical virus (the minute virus of mice) plays an architectural role by anisotropically increasing the mechanical stiffness of the virus. A finite element model predicted that this mechanical reinforcement is a consequence of the interaction between crystallographically visible, short DNA patches and the inner capsid wall. We have now tested this model by using protein engineering. Selected amino acid side chains have been truncated to specifically remove major interactions between the capsid and the visible DNA patches, and the effect of the mutations on the stiffness of virus particles has been measured using atomic force microscopy. The mutations do not affect the stiffness of the empty capsid; however, they significantly reduce the difference in stiffness between the DNA-filled virion and the empty capsid. The results (i) reveal that intermolecular interactions between individual chemical groups contribute to the mechanical properties of a supramolecular assembly and (ii) identify specific protein–DNA interactions as the origin of the anisotropic increase in the rigidity of a virus. This study also demonstrates that it is possible to control the mechanical properties of a protein nanoparticle by the rational application of protein engineering based on a mechanical model.

Footnotes

^‡To whom correspondence may be addressed: E-mail: mgarcia{at}cbm.uam.es or p.j.depablo{at}uam.es
Author contributions: C.C. and M.C. contributed equally to this work; P.J.d.P. and M.G.M. designed research; C.C. and M.C. performed research; C.C., M.C., P.J.d.P., and M.G.M. analyzed data; and M.G.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0708017105/DC1.