Structural insights into the regulation of RyR1 by S100A1.

ABSTRACT: S100A1, a small homodimeric EF-hand Ca²⁺-binding protein (~21 kDa), plays an important regulatory role in Ca²⁺ signaling pathways involved in various biological functions including Ca²⁺ cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca²⁺ release channel (~2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to RyR1, the skeletal muscle isoform, in absence and presence of Ca²⁺. Ca²⁺-free apo-S100A1 binds beneath the bridging solenoid (BSol) and forms contacts with the junctional solenoid and the shell-core linker of RyR1. Upon Ca²⁺-binding, S100

SUBMITTER: Weninger G 

PROVIDER: S-EPMC11228480 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature