文章基本信息

标题：Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
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作者：Luigi Russo ; Karin Giller ; Edith Pfitzner 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
页码：16845
DOI：10.1038/s41598-017-17088-5
语种：English
出版社：Springer Nature
摘要：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/ Leu794-Gly814-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1257-385/STAT6783-814 complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6783-814 peptide binds with additional N-terminal amino acids to NCoA1257-385, compared to the STAT6794-814 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.