Structure of the unique tetrameric STENOFOLIA homeodomain bound with DNA
Homeobox transcription factors are key regulators of morphogenesis and development in both animals and plants1. In plants, the WUSCHEL-related homeobox (WOX) family transcription factors function as central organizers of several developmental programs from embryo patterning to meristematic stem cell maintenance through transcriptional activation and repression2-4. The structure of WOX Homeodomain (HD) and the molecular mechanism of its interaction with DNA are unknown. Here, we report the 2.1 [A] crystal structure of the STENOFOLIA (STF) HD from Medicago truncatula in complex with DNA. STF binds DNA as a novel cooperative tetramer, enclosing nearly entire bound DNA surface. The STF tetramer is partially stabilized by docking of the C-terminal tail from one protomer onto a conserved hydrophobic surface on the head of another in a head-to-tail manner. Helix 3 not only serves a canonical role as a base reader in the major groove, but also provides extensive binding to DNA in the minor groove. Our structural and functional data reveal that STF specifically targets TGA sequence and the cooperative tetrameric binding with DNA is key to transcriptional repression in plants. Our data reveal an unprecedented HD:DNA recognition mechanism, representing the first plant HD structure from WOX family of transcription factors.