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Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy
Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Because many of these systems are highly dynamical, characterizing their movements is also a crucial step to unravel their biological functi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954442/ https://www.ncbi.nlm.nih.gov/pubmed/29642030 http://dx.doi.org/10.1016/j.bpj.2018.02.028 |
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author | Bonomi, Massimiliano Pellarin, Riccardo Vendruscolo, Michele |
author_facet | Bonomi, Massimiliano Pellarin, Riccardo Vendruscolo, Michele |
author_sort | Bonomi, Massimiliano |
collection | PubMed |
description | Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Because many of these systems are highly dynamical, characterizing their movements is also a crucial step to unravel their biological functions. To achieve this goal, we report an integrative modeling approach to simultaneously determine structure and dynamics of macromolecular systems from cryo-electron microscopy density maps. By quantifying the level of noise in the data and dealing with their ensemble-averaged nature, this approach enables the integration of multiple sources of information to model ensembles of structures and infer their populations. We illustrate the method by characterizing structure and dynamics of the integral membrane receptor STRA6, thus providing insights into the mechanisms by which it interacts with retinol binding protein and translocates retinol across the membrane. |
format | Online Article Text |
id | pubmed-5954442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59544422019-04-10 Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy Bonomi, Massimiliano Pellarin, Riccardo Vendruscolo, Michele Biophys J Proteins Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Because many of these systems are highly dynamical, characterizing their movements is also a crucial step to unravel their biological functions. To achieve this goal, we report an integrative modeling approach to simultaneously determine structure and dynamics of macromolecular systems from cryo-electron microscopy density maps. By quantifying the level of noise in the data and dealing with their ensemble-averaged nature, this approach enables the integration of multiple sources of information to model ensembles of structures and infer their populations. We illustrate the method by characterizing structure and dynamics of the integral membrane receptor STRA6, thus providing insights into the mechanisms by which it interacts with retinol binding protein and translocates retinol across the membrane. The Biophysical Society 2018-04-10 2018-04-10 /pmc/articles/PMC5954442/ /pubmed/29642030 http://dx.doi.org/10.1016/j.bpj.2018.02.028 Text en © 2018 Biophysical Society. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Proteins Bonomi, Massimiliano Pellarin, Riccardo Vendruscolo, Michele Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title | Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title_full | Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title_fullStr | Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title_full_unstemmed | Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title_short | Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy |
title_sort | simultaneous determination of protein structure and dynamics using cryo-electron microscopy |
topic | Proteins |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954442/ https://www.ncbi.nlm.nih.gov/pubmed/29642030 http://dx.doi.org/10.1016/j.bpj.2018.02.028 |
work_keys_str_mv | AT bonomimassimiliano simultaneousdeterminationofproteinstructureanddynamicsusingcryoelectronmicroscopy AT pellarinriccardo simultaneousdeterminationofproteinstructureanddynamicsusingcryoelectronmicroscopy AT vendruscolomichele simultaneousdeterminationofproteinstructureanddynamicsusingcryoelectronmicroscopy |