5nwm

Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6

spinqualitylabelsall models 5nwm, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5nwm is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: NCOA1, BHLHE74, SRC1 (HUMAN), STAT6 (HUMAN) Activity: Histone acetyltransferase, with EC number 2.3.1.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NCOA1_HUMAN] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. Function [NCOA1_HUMAN] 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. [STAT6_HUMAN] Carries out a dual function: signal transduction and activation of transcription. Involved in interleukin-4 signalling. Publication Abstract from PubMed Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STAT6 with nuclear coactivator 1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite the availability of an X-ray structure of the PAS-B domain/ Leu(794)-Gly(814)-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1(257-385)/STAT6(783-814) complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6(783-814) peptide binds with additional N-terminal amino acids to NCoA1(257-385), compared to the STAT6(794-814) peptide, explaining its higher affinity. Secondary and tertiary structures existing in the free peptide are more highly populated in the complex, suggesting binding by conformational selection. Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6.,Russo L, Giller K, Pfitzner E, Griesinger C, Becker S Sci Rep. 2017 Dec 4;7(1):16845. doi: 10.1038/s41598-017-17088-5. PMID:29203888 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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