SKN-1 domain folding and basic region monomer stabilization upon DNA binding

Adam S. Carroll, Dara E. Gilbert, Xiaoying Liu, Jim W. Cheung, Jennifer E. Michnowicz, Gerhard Wagner, Tom E. Ellenberger, T. Keith Blackwell

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The SKN-1 transcription factor specifies early embryonic cell fates in Caenorhabditis elegans. SKN-1 binds DNA at high affinity as a monomer, by means of a basic region like those of basic-leucine zipper (bZIP) proteins, which bind DNA only as dimers. We have investigated how the SKN-1 DNA- binding domain (the Skn domain) promotes stable binding of a basic region monomer to DNA. A flexible arm at the Skn domain amino terminus binds in the minor groove, but a support segment adjacent to the carboxy-terminal basic region can independently stabilize basic region-DNA binding. Off DNA, the basic region and arm are unfolded and, surprisingly, the support segment forms a molten globule of four α-helices. On binding DNA, the Skn domain adopts a tertiary structure in which the basic region helix extends directly from a support segment α-helix, which is required for binding. The remainder of the support segment anchors this uninterrupted helix on DNA, but leaves the basic region exposed in the major groove. This is similar to how the bZIP basic region extends from the leucine zipper, indicating that positioning and cooperative stability provided by helix extension are conserved mechanisms that promote binding of basic regions to DNA.

Original languageEnglish
Pages (from-to)2227-2238
Number of pages12
JournalGenes and Development
Volume11
Issue number17
DOIs
StatePublished - Sep 1 1997

Keywords

  • BZIP
  • Basic region
  • DNA binding
  • Molten globule
  • SKN-1
  • α-helix

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    Carroll, A. S., Gilbert, D. E., Liu, X., Cheung, J. W., Michnowicz, J. E., Wagner, G., Ellenberger, T. E., & Blackwell, T. K. (1997). SKN-1 domain folding and basic region monomer stabilization upon DNA binding. Genes and Development, 11(17), 2227-2238. https://doi.org/10.1101/gad.11.17.2227