A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1

Vikram Narayan, Petr Halada, Lenka Hernychová, Yuh Ping Chong, Jitka Žáková, Ted R Hupp, Borivoj Vojtesek, Kathryn L Ball (Lead / Corresponding author)

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    Abstract

    The interferon-regulated transcription factor and tumor suppressor protein IRF-1 is predicted to be largely disordered outside of the DNA-binding domain. One of the advantages of intrinsically disordered protein domains is thought to be their ability to take part in multiple, specific but low affinity protein interactions; however, relatively few IRF-1-interacting proteins have been described. The recent identification of a functional binding interface for the E3-ubiquitin ligase CHIP within the major disordered domain of IRF-1 led us to ask whether this region might be employed more widely by regulators of IRF-1 function. Here we describe the use of peptide aptamer-based affinity chromatography coupled with mass spectrometry to define a multiprotein binding interface on IRF-1 (Mf2 domain; amino acids 106-140) and to identify Mf2-binding proteins from A375 cells. Based on their function as known transcriptional regulators, a selection of the Mf2 domain-binding proteins (NPM1, TRIM28, and YB-1) have been validated using in vitro and cell-based assays. Interestingly, although NPM1, TRIM28, and YB-1 all bind to the Mf2 domain, they have differing amino acid specificities, demonstrating the degree of combinatorial diversity and specificity available through linear interaction motifs.
    Original languageEnglish
    Pages (from-to)14291-14303
    Number of pages13
    JournalJournal of Biological Chemistry
    Volume286
    Issue number16
    DOIs
    Publication statusPublished - 22 Apr 2011

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  • Cite this

    Narayan, V., Halada, P., Hernychová, L., Chong, Y. P., Žáková, J., Hupp, T. R., Vojtesek, B., & Ball, K. L. (2011). A multiprotein binding interface in an intrinsically disordered region of the tumor suppressor protein interferon regulatory factor-1. Journal of Biological Chemistry, 286(16), 14291-14303. https://doi.org/10.1074/jbc.M110.204602