Structural Basis for the Modulation of Ryanodine Receptors.

TitleStructural Basis for the Modulation of Ryanodine Receptors.
Publication TypeJournal Article
Year of Publication2021
AuthorsGong, D, Yan, N, Ledford, HA
JournalTrends Biochem Sci
Volume46
Issue6
Pagination489-501
Date Published2021 06
ISSN0968-0004
KeywordsCalcium, Calmodulin, Cryoelectron Microscopy, Microscopy, Electron, Ryanodine Receptor Calcium Release Channel
Abstract

<p>Historically, ryanodine receptors (RyRs) have presented unique challenges for high-resolution structural determination despite long-standing interest in their role in excitation-contraction coupling. Owing to their large size (nearly 2.2 MDa), high-resolution structures remained elusive until the advent of cryogenic electron microscopy (cryo-EM) techniques. In recent years, structures for both RyR1 and RyR2 have been solved at near-atomic resolution. Furthermore, recent reports have delved into their more complex structural associations with key modulators - proteins such as the dihydropyridine receptor (DHPR), FKBP12/12.6, and calmodulin (CaM), as well as ions and small molecules including Ca, ATP, caffeine, and PCB95. This review addresses the modulation of RyR1 and RyR2, in addition to the impact of such discoveries on intracellular Ca dynamics and biophysical properties.</p>

DOI10.1016/j.tibs.2020.11.009
Alternate JournalTrends Biochem Sci
PubMed ID33353849