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Potoyan, D.A.; Zheng, W.; Ferreiro, D.U.; Wolynes, P.G.; Komives, E.A. "PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites" (2016) Journal of Physical Chemistry B. 120(33):8532-8538
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Abstract:

We recently proposed a model for IκBα-mediated molecular stripping of NFκB from transcription sites. IκBα was shown experimentally to form a transient ternary complex with DNA-bound NFκB, but the mechanism by which the IκBα accelerates dissociation of the NFκB from the DNA was unknown. In this paper we construct and compute free energy profiles for the wild-type IκBα-mediated molecular stripping reaction of NFκB from DNA and compare with that for a mutant of IκBα bearing a charge-neutralized PEST. The differences in the free energy profile for stripping originate from the frustrated electrostatic interactions between the negatively charged PEST and the DNA. The PEST occupies two different conformations in the NFκB-IκBα binary complex, one of which occupies the DNA-binding cavity. Specific interactions with positively charged residues in the N-terminal domains of both p50 and p65 apparently draw the domains closer together hindering reassociation of DNA. Comparison with the charge-neutralized mutant reveals that all of these functional consequences result from the negative charges in the PEST sequence of IκBα. © 2016 American Chemical Society.

Registro:

Documento: Artículo
Título:PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites
Autor:Potoyan, D.A.; Zheng, W.; Ferreiro, D.U.; Wolynes, P.G.; Komives, E.A.
Filiación:Center for Theoretical Biological Physics, Department of Chemistry, Rice University, Houston, TX 77005, United States
Protein Physiology Lab, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA-CONICET-IQUIBICEN, Buenos Aires, C1430EGA, Argentina
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, San Diego, CA 92093-0378, United States
Palabras clave:Bins; Free energy; Transcription; Binary complexes; DNA transcriptions; N-terminal domains; Negative charge; Negatively charged; Positively charged; Specific interaction; Ternary complex; DNA; DNA; I kappa B kinase alpha; immunoglobulin enhancer binding protein; chemistry; computer simulation; genetic transcription; metabolism; molecular model; protein domain; Computer Simulation; DNA; Models, Molecular; NF-kappa B; NF-KappaB Inhibitor alpha; Protein Domains; Transcription, Genetic
Año:2016
Volumen:120
Número:33
Página de inicio:8532
Página de fin:8538
DOI: http://dx.doi.org/10.1021/acs.jpcb.6b02359
Título revista:Journal of Physical Chemistry B
Título revista abreviado:J Phys Chem B
ISSN:15206106
CODEN:JPCBF
CAS:DNA, 9007-49-2; I kappa B kinase alpha, 151217-48-0; DNA; NF-kappa B; NF-KappaB Inhibitor alpha
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v120_n33_p8532_Potoyan

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Citas:

---------- APA ----------
Potoyan, D.A., Zheng, W., Ferreiro, D.U., Wolynes, P.G. & Komives, E.A. (2016) . PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites. Journal of Physical Chemistry B, 120(33), 8532-8538.
http://dx.doi.org/10.1021/acs.jpcb.6b02359
---------- CHICAGO ----------
Potoyan, D.A., Zheng, W., Ferreiro, D.U., Wolynes, P.G., Komives, E.A. "PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites" . Journal of Physical Chemistry B 120, no. 33 (2016) : 8532-8538.
http://dx.doi.org/10.1021/acs.jpcb.6b02359
---------- MLA ----------
Potoyan, D.A., Zheng, W., Ferreiro, D.U., Wolynes, P.G., Komives, E.A. "PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites" . Journal of Physical Chemistry B, vol. 120, no. 33, 2016, pp. 8532-8538.
http://dx.doi.org/10.1021/acs.jpcb.6b02359
---------- VANCOUVER ----------
Potoyan, D.A., Zheng, W., Ferreiro, D.U., Wolynes, P.G., Komives, E.A. PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites. J Phys Chem B. 2016;120(33):8532-8538.
http://dx.doi.org/10.1021/acs.jpcb.6b02359