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The intrinsically disordered TC‐1 interacts with Chibby via regions with high helical propensity
Author(s) -
Gall Chris,
Xu Hanyu,
Brickenden Anne,
Ai Xuanjun,
Choy Wing Yiu
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.073062707
Subject(s) - wnt signaling pathway , biology , protein–protein interaction , intrinsically disordered proteins , beta catenin , nuclear magnetic resonance spectroscopy , catenin , regulator , signal transduction , biophysics , microbiology and biotechnology , gene , chemistry , biochemistry , stereochemistry
Thyroid cancer 1 (TC‐1) is a 106‐residue naturally disordered protein that has been found to associate with thyroid, gastric, and breast cancers. Recent studies showed that the protein functions as a positive regulator in the Wnt/β‐catenin signaling pathway, a pathway that is known to play essential roles in developmental processes and causes tumor formation when misregulated. By competing with β‐catenin for binding to Chibby (Cby), a conserved nuclear protein that antagonizes the β‐catenin–mediated transcriptions, TC‐1 up‐regulates a number of β‐catenin target genes that are known to be involved in the aggressive behavior of cancers. In order to gain a molecular understanding of the role TC‐1 plays in regulating the Wnt/β‐catenin signaling pathway, detailed structural studies of the protein and its interaction with Cby are essential. In this work, we used nuclear magnetic resonance (NMR) spectroscopy to elucidate the structure of TC‐1 and its interaction with Cby. Our results indicate that even though TC‐1 is naturally disordered, the protein adopts fairly compact conformations under nondenaturing conditions. Chemical shift analysis and relaxation measurements show that three regions (D44‐R53, K58‐A64, and D73‐T88) with high‐helical propensity are present in the C‐terminal portion of TC‐1. Upon addition of Cby, significant broadening of resonance signals derived from these helical regions of TC‐1 was observed. The result indicates that the intrinsically disordered TC‐1 interacts with Cby via its transient helical structure.