Formation of a structurally-stable conformation by the intrinsically disordered MYC:TRRAP complex

English version

Autoři: Edmond J. Feris ^aff001; John W. Hinds ^aff001; Michael D. Cole ^aff001
Působiště autorů: Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH, United States of America ^aff001; Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States of America ^aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225784

Souhrn

Our primary goal is to therapeutically target the oncogenic transcription factor MYC to stop tumor growth and cancer progression. Here, we report aspects of the biophysical states of the MYC protein and its interaction with one of the best-characterized MYC cofactors, TRansactivation/tRansformation-domain Associated Protein (TRRAP). The MYC:TRRAP interaction is critical for MYC function in promoting cancer. The interaction between MYC and TRRAP occurs at a precise region in the MYC protein, called MYC Homology Box 2 (MB2), which is central to the MYC transactivation domain (TAD). Although the MYC TAD is inherently disordered, this report suggests that MB2 may acquire a defined structure when complexed with TRRAP which could be exploited for the investigation of inhibitors of MYC function by preventing this protein-protein interaction (PPI). The MYC TAD, and in particular the MB2 motif, is unique and invariant in evolution, suggesting that MB2 is an ideal site for inhibiting MYC function.

Klíčová slova:

Transcription factors – Protein interactions – Protein domains – Carcinogenesis – Protein structure – Protein structure prediction – Ethylene – Glycols

Zdroje

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Formation of a structurally-stable conformation by the intrinsically disordered MYC:TRRAP complex

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