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@article{1607006,
author = {Kubáň, Vojtěch and Srb, Pavel and Štégnerová, Hana and Padrta, Petr and Zachrdla, Milan and Jaseňáková, Zuzana and Sanderova, H. and Vitovska, D. and Krasny, L. and Koval, T. and Dohnalek, J. and ZiemskaandLegiecka, J. and Grynberg, M. and Jarnot, P. and Gruca, A. and Jensen, M.R. and Blackledge, M. and Žídek, Lukáš},
article_location = {Washington},
article_number = {42},
doi = {http://dx.doi.org/10.1021/jacs.9b07837},
keywords = {RESIDUAL DIPOLAR COUPLINGS; BACILLUS-SUBTILIS; GENE-EXPRESSION; RAPID CHANGES; PROTEINS; NMR; TRANSCRIPTION; DETERMINANTS; PREDICTION; SCATTERING},
language = {eng},
issn = {0002-7863},
journal = {Journal of the American Chemical Society},
title = {Quantitative Conformational Analysis of Functionally Important Electrostatic Interactions in the Intrinsically Disordered Region of Delta Subunit of Bacterial RNA Polymerase},
url = {https://pubs.acs.org/doi/10.1021/jacs.9b07837},
volume = {141},
year = {2019}
}
TY - JOUR
ID - 1607006
AU - Kubáň, Vojtěch - Srb, Pavel - Štégnerová, Hana - Padrta, Petr - Zachrdla, Milan - Jaseňáková, Zuzana - Sanderova, H. - Vitovska, D. - Krasny, L. - Koval, T. - Dohnalek, J. - Ziemska-Legiecka, J. - Grynberg, M. - Jarnot, P. - Gruca, A. - Jensen, M.R. - Blackledge, M. - Žídek, Lukáš
PY - 2019
TI - Quantitative Conformational Analysis of Functionally Important Electrostatic Interactions in the Intrinsically Disordered Region of Delta Subunit of Bacterial RNA Polymerase
JF - Journal of the American Chemical Society
VL - 141
IS - 42
SP - 16817-16828
EP - 16817-16828
PB - American Chemical Society
SN - 00027863
KW - RESIDUAL DIPOLAR COUPLINGS
KW - BACILLUS-SUBTILIS
KW - GENE-EXPRESSION
KW - RAPID CHANGES
KW - PROTEINS
KW - NMR
KW - TRANSCRIPTION
KW - DETERMINANTS
KW - PREDICTION
KW - SCATTERING
UR - https://pubs.acs.org/doi/10.1021/jacs.9b07837
L2 - https://pubs.acs.org/doi/10.1021/jacs.9b07837
N2 - Electrostatic interactions play important roles in the functional mechanisms exploited by intrinsically disordered proteins (IDPs). The atomic resolution description of long-range and local structural propensities that can both be crucial for the function of highly charged IDPs presents significant experimental challenges. Here, we investigate the conformational behavior of the delta subunit of RNA polymerase from Bacillus subtilis whose unfolded domain is highly charged, with 7 positively charged amino acids followed by 51 acidic amino acids. Using a specifically designed analytical strategy, we identify transient contacts between the two regions using a combination of NMR paramagnetic relaxation enhancements, residual dipolar couplings (RDCs), chemical shifts, and small-angle scattering. This strategy allows the resolution of long-range and local ensemble averaged structural contributions to the experimental RDCs, and reveals that the negatively charged segment folds back onto the positively charged strand, compacting the conformational sampling of the protein while remaining highly flexible in solution. Mutation of the positively charged region abrogates the long-range contact, leaving the disordered domain in an extended conformation, possibly due to local repulsion of like-charges along the chain. Remarkably, in vitro studies show that this mutation also has a significant effect on transcription activity, and results in diminished cell fitness of the mutated bacteria in vivo. This study highlights the importance of accurately describing electrostatic interactions for understanding the functional mechanisms of IDPs.
ER -
KUBÁŇ, Vojtěch, Pavel SRB, Hana ŠTÉGNEROVÁ, Petr PADRTA, Milan ZACHRDLA, Zuzana JASEŇÁKOVÁ, H. SANDEROVA, D. VITOVSKA, L. KRASNY, T. KOVAL, J. DOHNALEK, J. ZIEMSKA-LEGIECKA, M. GRYNBERG, P. JARNOT, A. GRUCA, M.R. JENSEN, M. BLACKLEDGE and Lukáš ŽÍDEK. Quantitative Conformational Analysis of Functionally Important Electrostatic Interactions in the Intrinsically Disordered Region of Delta Subunit of Bacterial RNA Polymerase. \textit{Journal of the American Chemical Society}. Washington: American Chemical Society, 2019, vol.~141, No~42, p.~16817-16828. ISSN~0002-7863. Available from: https://dx.doi.org/10.1021/jacs.9b07837.
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