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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...

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Detalles Bibliográficos
Autores principales: Bonomi, Massimiliano, Pellarin, Riccardo, Vendruscolo, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2018
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
Descripción
Sumario: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.