RyR1-related myopathy mutations in ATP and calcium binding sites impair channel regulation.

ABSTRACT: The type 1 ryanodine receptor (RyR1) is an intracellular calcium (Ca²⁺) release channel on the sarcoplasmic/endoplasmic reticulum that is required for skeletal muscle contraction. RyR1 channel activity is modulated by ligands, including the activators Ca²⁺ and ATP. Patients with inherited mutations in RyR1 may exhibit muscle weakness as part of a heterogeneous, complex disorder known as RYR1-related myopathy (RYR1-RM) or more recently termed RYR1-related disorders (RYR1-RD). Guided by high-resolution structures of skeletal muscle RyR1, obtained using cryogenic electron microscopy, we introduced mutations into putative Ca²⁺ and ATP binding sites and studied the function of the resulting mutant channels. These mutations confirmed the functional significance o

SUBMITTER: Yuan Q 

PROVIDER: S-EPMC8609856 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature