Functional Pathways of Biomolecules Retrieved from Single-particle Snapshots
Open Access
- 30 March 2018
- preprint content
- preprint
- Published by Cold Spring Harbor Laboratory
- p. 291922
- https://doi.org/10.1101/291922
Abstract
We present a new approach to determining the conformational changes associated with biological function, and demonstrate its capabilities in the context of experimental single-particle cryo-EM snapshots of ryanodine receptor (RyR1), a Ca2+-channel involved in skeletal muscle excitation/contraction coupling. These results include the detailed conformational motions associated with functional paths including transitions between energy landscapes. The functional motions differ substantially from those inferred from discrete structures, shedding new light on the gating mechanism in RyR1. The differences include the conformationally active structural domains, the nature, sequence, and extent of conformational motions involved in function, and the way allosteric signals are transduced within and between domains. The approach is general, and applicable to a wide range of systems and processes.Keywords
This publication has 38 references indexed in Scilit:
- Structural Basis for Gating and Activation of RyR1Cell, 2016
- Structural insights into Ca2+-activated long-range allosteric channel gating of RyR1Cell Research, 2016
- Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolutionNature, 2014
- Structure of a mammalian ryanodine receptorNature, 2014
- Architecture and conformational switch mechanism of the ryanodine receptorNature, 2014
- Trajectories of the ribosome as a Brownian nanomachineProceedings of the National Academy of Sciences of the United States of America, 2014
- RELION: Implementation of a Bayesian approach to cryo-EM structure determinationJournal of Structural Biology, 2012
- A Bayesian View on Cryo-EM Structure DeterminationJournal of Molecular Biology, 2012
- Energy Landscapes as a Tool to Integrate GPCR Structure, Dynamics, and FunctionPhysiology, 2010
- Diffusion mapsApplied and Computational Harmonic Analysis, 2006