Research ArticleStructural Biology

A cryo-EM–based model of phosphorylation- and FKBP12.6-mediated allosterism of the cardiac ryanodine receptor

See allHide authors and affiliations

Sci. Signal.  23 May 2017:
Vol. 10, Issue 480, eaai8842
DOI: 10.1126/scisignal.aai8842

You are currently viewing the editor's summary.

View Full Text

More flexible with phosphorylation?

The type 2 ryanodine receptor (RyR2) mediates Ca2+ release from the sarcoplasmic reticulum of cardiomyocytes to initiate cardiac muscle contraction. Mutations in this intracellular Ca2+ channel are associated with cardiac diseases that may lead to heart failure. Dhindwal et al. used cryo-EM to determine the structure of rabbit RyR2 in complex with the regulatory protein FKBP12.6 in the closed state at 11.8 Å resolution. They found two conformations of RyR2, which may correspond to the extent of phosphorylation of a domain that harbors several disease-associated mutations. Because the more flexible conformation may correspond to phosphorylated RyR2, the authors suggest that phosphorylation may reduce the energy required for the Ca2+ channel to transition to an open state. These results provide a structural basis for understanding how phosphorylation may affect the activation of RyR2.