Viral mutations enhance the Max binding properties of the vMyc b-HLH-LZ domain

D. H. Crouch, F. Fisher, S. A. La Rocca, C. R. Goding, D. A. F. Gillespie

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    Abstract

    THE SPECIAL CHARACTERS IN THIS ABSTRACT CANNOT BE DISPLAYED CORRECTLY ON THIS PAGE. PLEASE REFER TO THE ABSTRACT ON THE PUBLISHER'S WEBSITE FOR AN ACCURATE DISPLAY. Interaction with Max via the helix–loop–helix/leucine zipper (HLH-LZ) domain is essential for Myc to function as a transcription factor. Myc is commonly upregulated in tumours, however, its activity can also be potentiated by virally derived mutations. vMyc, derived from the virus, MC29 gag-Myc, differs from its cellular counterpart by five amino acids. The N-terminal mutation stabilizes the protein, however, the significance of the other mutations is not known. We now show that vMyc can sustain longer deletions in the LZ domain than cMyc before complete loss in transforming activity, implicating the viral mutations in contributing to Myc:Max complex formation. We confirmed this both in vitro and in vivo, with loss of Max binding correlating with a loss in the biological activity of Myc. A specific viral mutation, isoleucine383>leucine (I383>L) in helix 2 of the HLH domain, extends the LZ domain from four to five heptad repeats. Significantly, introduction of I383>L into a Myc mutant that is defective for Max binding substantially restored its ability to complex with Max in vitro and in vivo. We therefore propose that this virally derived mutation is functional by significantly contributing to establishing amorehydrophobic interface between the LZs of Myc and Max.
    Original languageEnglish
    Pages (from-to)5235-5242
    Number of pages8
    JournalNucleic Acids Research
    Volume33
    Issue number16
    DOIs
    Publication statusPublished - Sep 2005

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  • Cite this

    Crouch, D. H., Fisher, F., La Rocca, S. A., Goding, C. R., & Gillespie, D. A. F. (2005). Viral mutations enhance the Max binding properties of the vMyc b-HLH-LZ domain. Nucleic Acids Research, 33(16), 5235-5242. https://doi.org/10.1093/nar/gki832