Functional Pathways of Biomolecules Retrieved from Single-particle Snapshots
Category
Published on
Type
posted-content
Author
Ali Dashti and Mrinal Shekhar and Danya Ben Hail and Ghoncheh Mashayekhi and Peter Schwander and Amedee des Georges and Joachim Frank and Abhishek Singharoy and Abbas Ourmazd
Citation
Dashti, A. et al., 2018. Functional Pathways of Biomolecules Retrieved from Single-particle Snapshots. Available at: http://dx.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.
DOI
Funding
NSF-STC Biology with X-ray Lasers (NSF-1231306)
