Cargando…

Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories

Site-directed spin labeling (SDSL) ESR is a valuable tool to probe protein systems that are not amenable to characterization by x-ray crystallography, NMR or EM. While general principles that govern the shape of SDSL ESR spectra are known, its precise relationship with protein structure and dynamics...

Descripción completa

Detalles Bibliográficos
Autores principales: Izmailov, Sergei A., Rabdano, Sevastyan O., Hasanbasri, Zikri, Podkorytov, Ivan S., Saxena, Sunil, Skrynnikov, Nikolai R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976580/
https://www.ncbi.nlm.nih.gov/pubmed/31969574
http://dx.doi.org/10.1038/s41598-019-56750-y
_version_ 1783490333435232256
author Izmailov, Sergei A.
Rabdano, Sevastyan O.
Hasanbasri, Zikri
Podkorytov, Ivan S.
Saxena, Sunil
Skrynnikov, Nikolai R.
author_facet Izmailov, Sergei A.
Rabdano, Sevastyan O.
Hasanbasri, Zikri
Podkorytov, Ivan S.
Saxena, Sunil
Skrynnikov, Nikolai R.
author_sort Izmailov, Sergei A.
collection PubMed
description Site-directed spin labeling (SDSL) ESR is a valuable tool to probe protein systems that are not amenable to characterization by x-ray crystallography, NMR or EM. While general principles that govern the shape of SDSL ESR spectra are known, its precise relationship with protein structure and dynamics is still not fully understood. To address this problem, we designed seven variants of GB1 domain bearing R1 spin label and recorded the corresponding MD trajectories (combined length 180 μs). The MD data were subsequently used to calculate time evolution of the relevant spin density matrix and thus predict the ESR spectra. The simulated spectra proved to be in good agreement with the experiment. Further analysis confirmed that the spectral shape primarily reflects the degree of steric confinement of the R1 tag and, for the well-folded protein such as GB1, offers little information on local backbone dynamics. The rotameric preferences of R1 side chain are determined by the type of the secondary structure at the attachment site. The rotameric jumps involving dihedral angles χ(1) and χ(2) are sufficiently fast to directly influence the ESR lineshapes. However, the jumps involving multiple dihedral angles tend to occur in (anti)correlated manner, causing smaller-than-expected movements of the R1 proxyl ring. Of interest, ESR spectra of GB1 domain with solvent-exposed spin label can be accurately reproduced by means of Redfield theory. In particular, the asymmetric character of the spectra is attributable to Redfield-type cross-correlations. We envisage that the current MD-based, experimentally validated approach should lead to a more definitive, accurate picture of SDSL ESR experiments.
format Online
Article
Text
id pubmed-6976580
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-69765802020-01-29 Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories Izmailov, Sergei A. Rabdano, Sevastyan O. Hasanbasri, Zikri Podkorytov, Ivan S. Saxena, Sunil Skrynnikov, Nikolai R. Sci Rep Article Site-directed spin labeling (SDSL) ESR is a valuable tool to probe protein systems that are not amenable to characterization by x-ray crystallography, NMR or EM. While general principles that govern the shape of SDSL ESR spectra are known, its precise relationship with protein structure and dynamics is still not fully understood. To address this problem, we designed seven variants of GB1 domain bearing R1 spin label and recorded the corresponding MD trajectories (combined length 180 μs). The MD data were subsequently used to calculate time evolution of the relevant spin density matrix and thus predict the ESR spectra. The simulated spectra proved to be in good agreement with the experiment. Further analysis confirmed that the spectral shape primarily reflects the degree of steric confinement of the R1 tag and, for the well-folded protein such as GB1, offers little information on local backbone dynamics. The rotameric preferences of R1 side chain are determined by the type of the secondary structure at the attachment site. The rotameric jumps involving dihedral angles χ(1) and χ(2) are sufficiently fast to directly influence the ESR lineshapes. However, the jumps involving multiple dihedral angles tend to occur in (anti)correlated manner, causing smaller-than-expected movements of the R1 proxyl ring. Of interest, ESR spectra of GB1 domain with solvent-exposed spin label can be accurately reproduced by means of Redfield theory. In particular, the asymmetric character of the spectra is attributable to Redfield-type cross-correlations. We envisage that the current MD-based, experimentally validated approach should lead to a more definitive, accurate picture of SDSL ESR experiments. Nature Publishing Group UK 2020-01-22 /pmc/articles/PMC6976580/ /pubmed/31969574 http://dx.doi.org/10.1038/s41598-019-56750-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Izmailov, Sergei A.
Rabdano, Sevastyan O.
Hasanbasri, Zikri
Podkorytov, Ivan S.
Saxena, Sunil
Skrynnikov, Nikolai R.
Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title_full Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title_fullStr Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title_full_unstemmed Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title_short Structural and dynamic origins of ESR lineshapes in spin-labeled GB1 domain: the insights from spin dynamics simulations based on long MD trajectories
title_sort structural and dynamic origins of esr lineshapes in spin-labeled gb1 domain: the insights from spin dynamics simulations based on long md trajectories
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976580/
https://www.ncbi.nlm.nih.gov/pubmed/31969574
http://dx.doi.org/10.1038/s41598-019-56750-y
work_keys_str_mv AT izmailovsergeia structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories
AT rabdanosevastyano structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories
AT hasanbasrizikri structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories
AT podkorytovivans structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories
AT saxenasunil structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories
AT skrynnikovnikolair structuralanddynamicoriginsofesrlineshapesinspinlabeledgb1domaintheinsightsfromspindynamicssimulationsbasedonlongmdtrajectories