Convergent views on disordered protein dynamics from NMR and
computational approaches

J 2022

Convergent views on disordered protein dynamics from NMR and computational approaches

SALVI, Nicola, Vojtěch ZAPLETAL, Zuzana JASEŇÁKOVÁ, Milan ZACHRDLA, Petr PADRTA et. al.

Basic information

Original name

Convergent views on disordered protein dynamics from NMR and computational approaches

Authors

SALVI, Nicola, Vojtěch ZAPLETAL (203 Czech Republic, belonging to the institution), Zuzana JASEŇÁKOVÁ (703 Slovakia, belonging to the institution), Milan ZACHRDLA, Petr PADRTA (203 Czech Republic, belonging to the institution), Subhash NARASIMHAN (356 India, belonging to the institution), Thorsten MARQUARDSEN, Jean-Max TYBURN, Lukáš ŽÍDEK (203 Czech Republic, belonging to the institution), Martin BLACKLEDGE, Fabien FERRAGE and Pavel KADEŘÁVEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

BIOPHYSICAL JOURNAL, UNITED STATES, CELL PRESS, 2022, 0006-3495

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.400

RIV identification code

RIV/00216224:14740/22:00126947

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.bpj.2022.09.016

UT WoS

000928435100005

Keywords in English

NMR; protein dynamics

Abstract

V originále

Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) is a class of biologically important proteins exhibiting specific biophysical characteristics. They lack a hydrophobic core, and their conformational behavior is strongly influenced by electrostatic interactions. IDPs and IDRs are highly dynamic, and a characterization of the motions of IDPs and IDRs is essential for their physically correct description. NMR together with molecular dynamics simulations are the methods best suited to such a task because they provide information about dynamics of proteins with atomistic resolution. Here, we present a study of motions of a disordered C-terminal domain of the delta subunit of RNA polymerase from Bacillus subtilis. Positively and negatively charged residues in the studied domain form transient electrostatic contacts critical for the biological function. Our study is focused on investigation of ps-ns dynamics of backbone of the delta subunit based on analysis of amide 15N NMR relaxation data and molecular dynamics simulations. In order to extend an informational content of NMR data to lower frequencies, which are more sensitive to slower motions, we combined standard (high-field) NMR relaxation experiments with high-resolution relaxometry. Altogether, we collected data reporting the relaxation at 12 different magnetic fields, resulting in an unprecedented data set. Our results document that the analysis of such data provides a consistent description of dynamics and confirms the validity of so far used protocols of the analysis of dynamics of IDPs also for a partially folded protein. In addition, the potential to access detailed description of motions at the timescale of tens of ns with the help of relaxometry data is discussed. Interestingly, in our case, it appears to be mostly relevant for a region involved in the formation of temporary contacts within the disordered region, which was previously proven to be biologically important.

Links

EF18_070/0009846, research and development project

Name: MSCAfellow2@MUNI

GJ18-04197Y, research and development project

Name: Charakterizace flexibilních oblastí RNA polymerázy Bacillus subtilis

Investor: Czech Science Foundation

90127, large research infrastructures

Name: CIISB II

Citovat

SALVI, Nicola, Vojtěch ZAPLETAL, Zuzana JASEŇÁKOVÁ, Milan ZACHRDLA, Petr PADRTA, Subhash NARASIMHAN, Thorsten MARQUARDSEN, Jean-Max TYBURN, Lukáš ŽÍDEK, Martin BLACKLEDGE, Fabien FERRAGE and Pavel KADEŘÁVEK. Convergent views on disordered protein dynamics from NMR and computational approaches. BIOPHYSICAL JOURNAL. UNITED STATES: CELL PRESS, 2022, vol. 121, No 20, p. 3785-3794. ISSN 0006-3495. Available from: https://dx.doi.org/10.1016/j.bpj.2022.09.016.

@article{2225678,
   author = {Salvi, Nicola and Zapletal, Vojtěch and Jaseňáková, Zuzana and Zachrdla, Milan and Padrta, Petr and Narasimhan, Subhash and Marquardsen, Thorsten and Tyburn, JeanandMax and Žídek, Lukáš and Blackledge, Martin and Ferrage, Fabien and Kadeřávek, Pavel},
   article_location = {UNITED STATES},
   article_number = {20},
   doi = {http://dx.doi.org/10.1016/j.bpj.2022.09.016},
   keywords = {NMR; protein dynamics},
   language = {eng},
   issn = {0006-3495},
   journal = {BIOPHYSICAL JOURNAL},
   title = {Convergent views on disordered protein dynamics from NMR and computational approaches},
   url = {https://linkinghub.elsevier.com/retrieve/pii/S0006-3495(22)00766-4},
   volume = {121},
   year = {2022}
}

TY  - JOUR
ID  - 2225678
AU  - Salvi, Nicola - Zapletal, Vojtěch - Jaseňáková, Zuzana - Zachrdla, Milan - Padrta, Petr - Narasimhan, Subhash - Marquardsen, Thorsten - Tyburn, Jean-Max - Žídek, Lukáš - Blackledge, Martin - Ferrage, Fabien - Kadeřávek, Pavel
PY  - 2022
TI  - Convergent views on disordered protein dynamics from NMR and computational approaches
JF  - BIOPHYSICAL JOURNAL
VL  - 121
IS  - 20
SP  - 3785-3794
EP  - 3785-3794
PB  - CELL PRESS
SN  - 00063495
KW  - NMR
KW  - protein dynamics
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0006-3495(22)00766-4
N2  - Intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) is a class of biologically important proteins exhibiting specific biophysical characteristics. They lack a hydrophobic core, and their conformational behavior is strongly influenced by electrostatic interactions. IDPs and IDRs are highly dynamic, and a characterization of the motions of IDPs and IDRs is essential for their physically correct description. NMR together with molecular dynamics simulations are the methods best suited to such a task because they provide information about dynamics of proteins with atomistic resolution. Here, we present a study of motions of a disordered C-terminal domain of the delta subunit of RNA polymerase from Bacillus subtilis. Positively and negatively charged residues in the studied domain form transient electrostatic contacts critical for the biological function. Our study is focused on investigation of ps-ns dynamics of backbone of the delta subunit based on analysis of amide 15N NMR relaxation data and molecular dynamics simulations. In order to extend an informational content of NMR data to lower frequencies, which are more sensitive to slower motions, we combined standard (high-field) NMR relaxation experiments with high-resolution relaxometry. Altogether, we collected data reporting the relaxation at 12 different magnetic fields, resulting in an unprecedented data set. Our results document that the analysis of such data provides a consistent description of dynamics and confirms the validity of so far used protocols of the analysis of dynamics of IDPs also for a partially folded protein. In addition, the potential to access detailed description of motions at the timescale of tens of ns with the help of relaxometry data is discussed. Interestingly, in our case, it appears to be mostly relevant for a region involved in the formation of temporary contacts within the disordered region, which was previously proven to be biologically important.
ER  -

SALVI, Nicola, Vojtěch ZAPLETAL, Zuzana JASEŇÁKOVÁ, Milan ZACHRDLA, Petr PADRTA, Subhash NARASIMHAN, Thorsten MARQUARDSEN, Jean-Max TYBURN, Lukáš ŽÍDEK, Martin BLACKLEDGE, Fabien FERRAGE and Pavel KADEŘÁVEK. Convergent views on disordered protein dynamics from NMR and computational approaches. \textit{BIOPHYSICAL JOURNAL}. UNITED STATES: CELL PRESS, 2022, vol.~121, No~20, p.~3785-3794. ISSN~0006-3495. Available from: https://dx.doi.org/10.1016/j.bpj.2022.09.016.

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