Role of intrinsically disordered protein regions/domains in transcriptional regulation.
In recent years, it has become quite evident that numerous proteins exist as an ensemble of conformers that collectively appears to be intrinsically disordered (ID). Of particular significance is the growing body of evidence that intrinsic disorder is found in disproportionately higher amounts in cell signaling proteins and transcription factors, suggesting an important role in their regulatory capacity. Since these proteins are known to possess specific regions/domains that interact with specific coregulatory proteins for their efficient functioning, the large flexible regions in this class of proteins may have an advantage over fully folded proteins that can allow them to make more efficient physical functional interactions with their target partners, which may represent a mechanism for regulation of cellular processes. In fact, recent studies from several laboratories have reported existence of ID sequences in such regions in signaling proteins that play a critical role in regulating their functions. There are reports showing that ID regions/domains commonly exist within proteins with modular structures such as transcription factors, and are often located in their transactivation domain. Therefore, it is important to find out their existence and functional roles in transcriptional regulations by transcription factors. In recent years there has been growing evidence suggesting that an induced fit process leads to imposition of folded functional structure in these ID protein regions/domains. In most cases such binding and folding events have been found to occur when ID region encounters its specific binding partner(s).
Garza
Anna S
AS
Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-0655, USA.
Ahmad
Nihal
N
Kumar
Raj
R
D000818:Animals; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014158:Transcription, Genetic