Transcriptional Regulators
The softest modes of motion of transcriptional regulators enable their interaction with DNA and RNA. Transcriptional regulators control gene expression by binding to specific DNA sequences near gene promoters or enhancers, playing crucial roles in development, differentiation, and response to the environment. Some can also interact with RNA, expanding their regulatory capabilities and contributing to the complex network of gene regulation.
The intrinsic dynamics of TR transcriptional regulators enable them to interact with RNA and DNA. For example, nucleolar protein 9 (NOP9)1 has an eleven-stranded pumilio repeat protein structure that facilitates RNA binding and maturation. The softest mode of unbound NOP9 almost entirely defines its conformational adaptation for RNA binding.
Investigation of the unbound and DNA-bound forms of a transcriptional regulator2 from Streptococcus thermophilus revealed a conformational transition, where the first ten modes cumulatively define around 70% of the difference between the unbound and DNA-bound forms of the transcription factor.
Burkholderia TALE-like protein 1 (BAT1)3, a TALE protein with 19 repeats that bind to DNA, lacks the common N-terminal and C-terminal structure of TALEs. Despite this, BAT1 can still bind to DNA, forming a superhelical structure, aided by a nuclear localization signal (NLS). The first four modes of motion of unbound BAT1 almost entirely define its conformational difference with the DNA-bound form.
References
1Zhang, J.; McCann, K. L.; Qiu, C.; Gonzalez, L. E.; Baserga, S. J.; Hall, T. M., Nop9 is a PUF-like protein that prevents premature cleavage to correctly process pre-18S rRNA. Nat Commun 2016, 7, 13085.
2Talagas, A.; Fontaine, L.; Ledesma-García, L.; Mignolet, J.; Li de la Sierra-Gallay, I.; Lazar, N.; Aumont-Nicaise, M.; Federle, M. J.; Prehna, G.; Hols, P.; Nessler, S., Structural Insights into Streptococcal Competence Regulation by the Cell-to-Cell Communication System ComRS. PLoS Pathog 2016, 12 (12), e1005980.
348. Zhang, B.; Han, X.; Yuan, W.; Zhang, H., TALEs as double-edged swords in plant-pathogen interactions: Progress, challenges, and perspectives. Plant Commun 2022, 3 (3), 100318.
