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PLoS One. 2014 May 19;9(5):e97975. doi: 10.1371/journal.pone.0097975. eCollection 2014.

Molecular dynamics simulation study of conformational changes of transcription factor TFIIS during RNA polymerase II transcriptional arrest and reactivation.

Author information

1
Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of America.
2
Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.
3
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
4
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, United States of America.
5
Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of America; Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America; Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America.

Abstract

Transcription factor IIS (TFIIS) is a protein known for catalyzing the cleavage reaction of the 3'-end of backtracked RNA transcript, allowing RNA polymerase II (Pol II) to reactivate the transcription process from the arrested state. Recent structural studies have provided a molecular basis of protein-protein interaction between TFIIS and Pol II. However, the detailed dynamic conformational changes of TFIIS upon binding to Pol II and the related thermodynamic information are largely unknown. Here we use computational approaches to investigate the conformational space of TFIIS in the Pol II-bound and Pol II-free (unbound) states. Our results reveal two distinct conformations of TFIIS: the closed and the open forms. The closed form is dominant in the Pol II-free (unbound) state of TFIIS, whereas the open form is favorable in the Pol II-bound state. Furthermore, we discuss the free energy difference involved in the conformational changes between the two forms in the presence or absence of Pol II. Additionally, our analysis indicates that hydrophobic interactions and the protein-protein interactions between TFIIS and Pol II are crucial for inducing the conformational changes of TFIIS. Our results provide novel insights into the functional interplay between Pol II and TFIIS as well as mechanism of reactivation of Pol II transcription by TFIIS.

PMID:
24842057
PMCID:
PMC4026522
DOI:
10.1371/journal.pone.0097975
[Indexed for MEDLINE]
Free PMC Article

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