Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.

TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simu...

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Autores principales:	Hua Wan, Jian-ping Hu, Kang-shun Li, Xu-hong Tian, Shan Chang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/94794f892bf741ae9a0cadc6fd82d371
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spelling	oai:doaj.org-article:94794f892bf741ae9a0cadc6fd82d3712021-11-18T08:51:39ZMolecular dynamics simulations of DNA-free and DNA-bound TAL effectors.1932-620310.1371/journal.pone.0076045https://doaj.org/article/94794f892bf741ae9a0cadc6fd82d3712013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24130757/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues) with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA), the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL). The conformational analysis of DNA indicates that the 5' end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism.Hua WanJian-ping HuKang-shun LiXu-hong TianShan ChangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76045 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hua Wan Jian-ping Hu Kang-shun Li Xu-hong Tian Shan Chang Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
description	TAL (transcriptional activator-like) effectors (TALEs) are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD) simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues) with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA), the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL). The conformational analysis of DNA indicates that the 5' end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism.
format	article
author	Hua Wan Jian-ping Hu Kang-shun Li Xu-hong Tian Shan Chang
author_facet	Hua Wan Jian-ping Hu Kang-shun Li Xu-hong Tian Shan Chang
author_sort	Hua Wan
title	Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
title_short	Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
title_full	Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
title_fullStr	Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
title_full_unstemmed	Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.
title_sort	molecular dynamics simulations of dna-free and dna-bound tal effectors.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/94794f892bf741ae9a0cadc6fd82d371
work_keys_str_mv	AT huawan moleculardynamicssimulationsofdnafreeanddnaboundtaleffectors AT jianpinghu moleculardynamicssimulationsofdnafreeanddnaboundtaleffectors AT kangshunli moleculardynamicssimulationsofdnafreeanddnaboundtaleffectors AT xuhongtian moleculardynamicssimulationsofdnafreeanddnaboundtaleffectors AT shanchang moleculardynamicssimulationsofdnafreeanddnaboundtaleffectors
_version_	1718421216137576448

Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.

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