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J Biol Chem. 2009 May 29;284(22):15184-92. doi: 10.1074/jbc.M808479200. Epub 2009 Mar 26.

Molecular basis of coiled coil coactivator recruitment by the aryl hydrocarbon receptor nuclear translocator (ARNT).

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  • 1Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.


The aryl hydrocarbon receptor nuclear translocator (ARNT) serves as the obligate heterodimeric partner for bHLH-PAS proteins involved in sensing and coordinating transcriptional responses to xenobiotics, hypoxia, and developmental pathways. Although its C-terminal transactivation domain is dispensable for transcriptional activation in vivo, ARNT has recently been shown to use its N-terminal bHLH and/or PAS domains to interact with several transcriptional coactivators that are required for transcriptional initiation after xenobiotic or hypoxic cues. Here we show that ARNT uses a single PAS domain to interact with two coiled coil coactivators, TRIP230 and CoCoA. Both coactivators interact with the same interface on the ARNT PAS-B domain, located on the opposite side of the domain used to associate with the analogous PAS domain on its heterodimeric bHLH-PAS partner HIF-2alpha. Using NMR and biochemical studies, we identified the ARNT-interacting motif of one coactivator, TRIP230 as an LXXLL-like nuclear receptor box. Mutation of this motif and proximal sequences disrupts the interaction with ARNT PAS-B. Identification of this ARNT-coactivator interface illustrates how ARNT PAS-B is used to form critical interactions with both bHLH-PAS partners and coactivators that are required for transcriptional responses.

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