Regulation of a viral proteinase by a peptide and DNA in one-dimensional space IV: Viral proteinase slides along dna to locate and process its substrates

Paul C. Blainey, Vito Graziano, Ana J. Pérez-Berná, William J. McGrath, S. Jane Flint, Carmen San Martín, X. Sunney Xie, Walter F. Mangel

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Background: The adenovirus proteinase and its precursor protein substrates are all sequence independentDNAbinding proteins. Results: The proteinase slides along DNA to locate and process its substrates. Conclusion: Processing of precursor proteins by the adenovirus proteinase occurs on DNA. Significance: This is a new way an enzyme not involved in nucleic acid metabolism interacts with its substrates: sliding onDNA via one-dimensional diffusion. Precursor proteins used in the assembly of adenovirus virions must be processed by the virally encoded adenovirus proteinase (AVP) before the virus particle becomes infectious. An activated adenovirus proteinase, the AVP-pVIc complex, was shown to slide along viral DNA with an extremely fast one-dimensional diffusion constant, 21.0 1.9-106 bp2/s. In principle, one-dimensional diffusion can provide a means for DNA-bound proteinases to locate and process DNA-bound substrates. Here, we show that this is correct. In vitro, AVP-pVIc complexes processed a purified virion precursor protein in a DNA-dependent reaction; in a quasi in vivo environment, heat-disrupted ts-1 virions, AVP-pVIc complexes processed five different precursor proteins in DNA-dependent reactions. Sliding of AVP-pVIc complexes along DNA illustrates a new biochemical mechanism by which a proteinase can locate its substrates, represents a new paradigm for virion maturation, and reveals a new way of exploiting the surface of DNA.

Original languageEnglish (US)
Pages (from-to)2092-2102
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number3
DOIs
StatePublished - Jan 18 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Blainey, P. C., Graziano, V., Pérez-Berná, A. J., McGrath, W. J., Flint, S. J., Martín, C. S., Xie, X. S., & Mangel, W. F. (2013). Regulation of a viral proteinase by a peptide and DNA in one-dimensional space IV: Viral proteinase slides along dna to locate and process its substrates. Journal of Biological Chemistry, 288(3), 2092-2102. https://doi.org/10.1074/jbc.M112.407460