Home LiteratureArticle Details
PMID: 18334651 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Manipulation of the mechanical properties of a virus by protein engineering.

Carrasco C, Castellanos M, de Pablo PJ, Mateu MG

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.

MeSH Terms
Microscopy, Atomic Force Minute Virus of Mice/chemistry,genetics,metabolism Models, Molecular Mutation/genetics Protein Engineering Viral Proteins/chemistry,genetics,metabolism,ultrastructure Virion/chemistry,metabolism,ultrastructure
Chemicals
Viral Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Carrasco Carolina
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.
Castellanos Milagros
de Pablo Pedro J
Mateu Mauricio G
References (48)
48 references, click to expand
  1. Double-helical RNA in satellite tobacco mosaic virus.
    Nature. 1993 Jan 14;361(6408):179-82 PMID: 8421525
  2. Functional relevance of amino acid residues involved in interactions with ordered nucleic acid in a spherical virus.
    J Biol Chem. 2005 May 6;280(18):17969-77 PMID: 15728575
  3. Nuclear export of the nonenveloped parvovirus virion is directed by an unordered protein signal exposed on the capsid surface.
    J Virol. 2004 Oct;78(19):10685-94 PMID: 15367635
  4. Controlled conformational transitions in the MVM virion expose the VP1 N-terminus and viral genome without particle disassembly.
    Virology. 1999 Feb 1;254(1):169-81 PMID: 9927584
  5. WSXM: a software for scanning probe microscopy and a tool for nanotechnology.
    Rev Sci Instrum. 2007 Jan;78(1):013705 PMID: 17503926
  6. Osmotic shock and the strength of viral capsids.
    Biophys J. 2003 Jul;85(1):70-4 PMID: 12829465
  7. Structural determinants of tissue tropism and in vivo pathogenicity for the parvovirus minute virus of mice.
    J Virol. 2005 Sep;79(17):10931-43 PMID: 16103145
  8. Protein-RNA interactions in an icosahedral virus at 3.0 A resolution.
    Science. 1989 Jul 14;245(4914):154-9 PMID: 2749253
  9. A conserved leucine that constricts the pore through the capsid fivefold cylinder plays a central role in parvoviral infection.
    Virology. 2004 Jun 1;323(2):243-56 PMID: 15193920
  10. Dissection of the effector-binding site and complementation studies of Escherichia coli phosphofructokinase using site-directed mutagenesis.
    Biochemistry. 1989 Aug 22;28(17):6841-7 PMID: 2531002
  11. Mechanical properties of viral capsids.
    Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Aug;72(2 Pt 1):021917 PMID: 16196614
  12. Functional implications of the structure of the murine parvovirus, minute virus of mice.
    Structure. 1998 Nov 15;6(11):1369-81 PMID: 9817841
  13. In vitro disassembly of a parvovirus capsid and effect on capsid stability of heterologous peptide insertions in surface loops.
    J Biol Chem. 2004 Feb 20;279(8):6517-25 PMID: 14660623
  14. Complementary roles of multiple nuclear targeting signals in the capsid proteins of the parvovirus minute virus of mice during assembly and onset of infection.
    J Virol. 2002 Jul;76(14):7049-59 PMID: 12072505
  15. Viruses: making friends with old foes.
    Science. 2006 May 12;312(5775):873-5 PMID: 16690856
  16. Mapping of the fibrotropic and lymphotropic host range determinants of the parvovirus minute virus of mice.
    J Virol. 1988 Aug;62(8):2605-13 PMID: 3392768
  17. Structure determination of minute virus of mice.
    Acta Crystallogr D Biol Crystallogr. 1997 Jan 1;53(Pt 1):93-102 PMID: 15299974
  18. RASMOL: biomolecular graphics for all.
    Trends Biochem Sci. 1995 Sep;20(9):374 PMID: 7482707
  19. Bacteriophage capsids: tough nanoshells with complex elastic properties.
    Proc Natl Acad Sci U S A. 2004 May 18;101(20):7600-5 PMID: 15133147
  20. Transcriptional inhibition of the parvovirus minute virus of mice by constitutive expression of an antisense RNA targeted against the NS-1 transactivator protein.
    Virology. 1995 Jan 10;206(1):57-68 PMID: 7831812
  21. The three-dimensional structure of canine parvovirus and its functional implications.
    Science. 1991 Mar 22;251(5000):1456-64 PMID: 2006420
  22. Ordered duplex RNA controls capsid architecture in an icosahedral animal virus.
    Nature. 1993 Jan 14;361(6408):176-9 PMID: 8421524
  23. Biochemical and physical characterization of parvovirus minute virus of mice virus-like particles.
    Virology. 2000 Feb 15;267(2):299-309 PMID: 10662625
  24. Role of interfacial amino acid residues in assembly, stability, and conformation of a spherical virus capsid.
    Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2724-9 PMID: 14981262
  25. WHAT IF: a molecular modeling and drug design program.
    J Mol Graph. 1990 Mar;8(1):52-6, 29 PMID: 2268628
  26. Origin of icosahedral symmetry in viruses.
    Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15556-60 PMID: 15486087
  27. A diversity of bacteriophage forms and genomes can be isolated from the surface sands of the Sahara Desert.
    Extremophiles. 2005 Aug;9(4):289-96 PMID: 15947866
  28. Protein-RNA interactions and virus stability as probed by the dynamics of tryptophan side chains.
    J Biol Chem. 2002 Dec 6;277(49):47596-602 PMID: 12359712
  29. Mechanics of DNA packaging in viruses.
    Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3173-8 PMID: 12629206
  30. DNA packaging and ejection forces in bacteriophage.
    Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13671-4 PMID: 11707588
  31. The structure of pariacoto virus reveals a dodecahedral cage of duplex RNA.
    Nat Struct Biol. 2001 Jan;8(1):77-83 PMID: 11135676
  32. Structural tolerance versus functional intolerance to mutation of hydrophobic core residues surrounding cavities in a parvovirus capsid.
    J Mol Biol. 2006 Jul 28;360(5):1081-93 PMID: 16814321
  33. DNA-mediated anisotropic mechanical reinforcement of a virus.
    Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13706-11 PMID: 16945903
  34. Mechanical properties of murine leukemia virus particles: effect of maturation.
    Biophys J. 2006 Jul 15;91(2):767-74 PMID: 16632508
  35. VP2 cleavage and the leucine ring at the base of the fivefold cylinder control pH-dependent externalization of both the VP1 N terminus and the genome of minute virus of mice.
    J Virol. 2006 Jan;80(1):161-71 PMID: 16352540
  36. Atomic structure of single-stranded DNA bacteriophage phi X174 and its functional implications.
    Nature. 1992 Jan 9;355(6356):137-43 PMID: 1370343
  37. The bacteriophage straight phi29 portal motor can package DNA against a large internal force.
    Nature. 2001 Oct 18;413(6857):748-52 PMID: 11607035
  38. High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis.
    Science. 1989 Jun 2;244(4908):1081-5 PMID: 2471267
  39. Osmotic pressure inhibition of DNA ejection from phage.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9292-5 PMID: 12881484
  40. Single-stranded DNA-protein interactions in canine parvovirus.
    Structure. 1995 Feb 15;3(2):151-62 PMID: 7735832
  41. RNA-protein interactions in spherical viruses.
    Arch Virol. 2002 Dec;147(12):2261-79 PMID: 12491096
  42. Internal DNA pressure modifies stability of WT phage.
    Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9603-8 PMID: 17535894
  43. To build a virus capsid. An equilibrium model of the self assembly of polyhedral protein complexes.
    J Mol Biol. 1994 Aug 5;241(1):59-67 PMID: 8051707
  44. Conformations, interactions, and thermostabilities of RNA and proteins in bean pod mottle virus: investigation of solution and crystal structures by laser Raman spectroscopy.
    Biochemistry. 1992 Jul 28;31(29):6673-82 PMID: 1637806
  45. Nanoindentation studies of full and empty viral capsids and the effects of capsid protein mutations on elasticity and strength.
    Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6184-9 PMID: 16606825
  46. Viruses in the sea.
    Nature. 2005 Sep 15;437(7057):356-61 PMID: 16163346
  47. Electrostatics and the assembly of an RNA virus.
    Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Jun;71(6 Pt 1):061928 PMID: 16089786
  48. A stiffness switch in human immunodeficiency virus.
    Biophys J. 2007 Mar 1;92(5):1777-83 PMID: 17158573
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2008-03-18
Epub
2008-00-11
Pages
4150-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2393779
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com