KIX domain is part of transcriptional coactivator CREB binding protein (CBP) which is an important part of the gene regulation. KIX domain is a structured globular protein that consists of three alpha-helices and provides two allosteric binding sites named after its characteristic binding partners – the MLL site and the c‑Myb site [1-2]. KIX domain binding partners are often unstructured and become folded only after interacting with the KIX domain. Despite its relatively small size (10 kDa), KIX domain serves as a great model protein for understanding molecular allostery, coupled folding and binding mechanisms of transactivation domains of intrinsically disordered proteins [3]. Recently established Nine amino acid Transactivation Domain (9aaTAD) motif unifies a prevalent number of transactivation domains of transcription factors [4]. This 9aaTAD pattern can be predicted using the prediction tool and can be further explored using the KIX domain and mutants of its typical binding partners.
This phenomenon was investigated by NMR spectroscopy 2D HN‑HSQC experiment using 15N isotopically labelled KIX domain titrated with MLL WT and its mutants to observe structural changes and dynamics.
This work was supported by Ministry of Education, Youth and Sports within programme INTER - ACTION (project No. LTAUSA18168). This research was financially supported by Ministry of Education, Youths and Sports of the Czech Republic within CEITEC 2020 (LQ1601) project.
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