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

  • 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.

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Metadaten
Author:Changsun Eun, Juan Manuel Ortiz-Sánchez, Lintai Da, Dong Wang, J. Andrew McCammon
URN:urn:nbn:de:hebis:30:3-338006
DOI:https://doi.org/10.1371/journal.pone.0097975
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/24842057
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2014/05/19
Date of first Publication:2014/05/19
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/05/23
Volume:9
Issue:(5):e97975
Page Number:8
Note:
Copyright: © 2014 Eun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:365158410
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0