PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites
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...
Guardado en:
| Autor principal: | |
|---|---|
| Publicado: |
2016
|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v120_n33_p8532_Potoyan http://hdl.handle.net/20.500.12110/paper_15206106_v120_n33_p8532_Potoyan |
| Aporte de: |
| id |
paper:paper_15206106_v120_n33_p8532_Potoyan |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_15206106_v120_n33_p8532_Potoyan2023-06-08T16:19:11Z PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites Ferreiro, Diego U. 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 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. Fil:Ferreiro, D.U. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v120_n33_p8532_Potoyan http://hdl.handle.net/20.500.12110/paper_15206106_v120_n33_p8532_Potoyan |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Ferreiro, Diego U. PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| topic_facet |
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 |
| description |
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. |
| author |
Ferreiro, Diego U. |
| author_facet |
Ferreiro, Diego U. |
| author_sort |
Ferreiro, Diego U. |
| title |
PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| title_short |
PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| title_full |
PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| title_fullStr |
PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| title_full_unstemmed |
PEST Control of Molecular Stripping of NFκB from DNA Transcription Sites |
| title_sort |
pest control of molecular stripping of nfκb from dna transcription sites |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v120_n33_p8532_Potoyan http://hdl.handle.net/20.500.12110/paper_15206106_v120_n33_p8532_Potoyan |
| work_keys_str_mv |
AT ferreirodiegou pestcontrolofmolecularstrippingofnfkbfromdnatranscriptionsites |
| _version_ |
1768544656251944960 |