An intrinsically disordered region of the transcription factor, NFAT5, becomes more ordered with an increase in osmolality (1182.8)

Hypertonicity stimulates NFAT5 nuclear localization and transactivating activity. Many transcription factors are known to contain intrinsically disordered regions (IDRs) which become more structured with local environmental changes such as osmolality, temperature and tonicity. The N-terminal region of NFAT5 is predicted to contain an IDR. Using far-UV CD and fluorescence we found that addition of the organic osmolyte trehalose to the purified N-terminal IDR of NFAT5 caused an increase in the structure of the IDR, consistent with a 2-state transition, ID to native. To investigate how this increased structure affects cellular protein-protein interactions, we looked for a correlation between change in structure and association with other proteins. Mass spectrometry identified NFAT5 IDR protein binding partners. We thus have demonstrated that a change in osmolality gives rise to an increase in IDR structure and affects NFAT5 protein-protein interactions. These data will aid in understanding transcriptional up...