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Crystal structure of the Nco-A1 PAS-B domain bound to the STAT6 transactivation domain LXXLL motif
Structural highlights
FunctionNCOA1_MOUSE Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedSignal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 (IL-4) by direct interaction with coactivators. The CREB-binding protein (p300/CBP) and the nuclear coactivator 1 (NCoA-1), a member of the p160/steroid receptor coactivator family, bind independently to specific regions of the STAT6 transactivation domain and act as coactivators. The interaction between STAT6 and NCoA-1 is mediated by an LXXLL motif in the transactivation domain of STAT6. To define the mechanism of coactivator recognition, we determined the crystal structure of the NCoA-1 PAS-B domain in complex with the STAT6 LXXLL motif. The amphipathic, alpha-helical STAT6 LXXLL motif binds mostly through specific hydrophobic interactions to NCoA-1. A single amino acid of the NCoA-1 PAS-B domain establishes hydrophilic interactions with the STAT6 peptide. STAT6 interacts only with the PAS-B domain of NCoA-1 but not with the homologous regions of NCoA-2 and NCoA-3. The residues involved in binding the STAT6 peptide are strongly conserved between the different NCoA family members. Therefore surface complementarity between the hydrophobic faces of the STAT6 fragment and of the NCoA-1 PAS-B domain almost exclusively defines the binding specificity between the two proteins. Structure of the NCoA-1/SRC-1 PAS-B domain bound to the LXXLL motif of the STAT6 transactivation domain.,Razeto A, Ramakrishnan V, Litterst CM, Giller K, Griesinger C, Carlomagno T, Lakomek N, Heimburg T, Lodrini M, Pfitzner E, Becker S J Mol Biol. 2004 Feb 13;336(2):319-29. PMID:14757047[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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