Department of Biochemistry & Molecular Biology School of Medicine University of Maryland, Baltimore, MD, USA.
Department of Biochemistry & Molecular Biology School of Medicine University of Maryland, Baltimore, MD, USA; Center for Biomolecular Therapeutics (CBT), Baltimore, MD, USA; Institute of Bioscience and Biotechnology Research (IBBR), Rockville, MD, USA.
Cell Calcium. 2024 Nov;123:102947. doi: 10.1016/j.ceca.2024.102947. Epub 2024 Aug 23.
S100A1, a calcium-binding protein, plays a crucial role in regulating Ca signaling pathways in skeletal and cardiac myocytes via interactions with the ryanodine receptor (RyR) to affect Ca release and contractile performance. Biophysical studies strongly suggest that S100A1 interacts with RyRs but have been inconclusive about both the nature of this interaction and its competition with another important calcium-binding protein, calmodulin (CaM). Thus, high-resolution cryo-EM studies of RyRs in the presence of S100A1, with or without additional CaM, were needed. The elegant work by Weninger et al. demonstrates the interaction between S100A1 and RyR1 through various experiments and confirms that S100A1 activates RyR1 at sub-micromolar Ca concentrations, increasing the open probability of RyR1 channels.
S100A1 是一种钙结合蛋白，通过与肌质网钙释放通道（ryanodine receptor，RyR）相互作用，在骨骼和心肌细胞中调节 Ca 信号通路，从而影响 Ca 释放和收缩性能。生物物理研究强烈表明 S100A1 与 RyR 相互作用，但对于这种相互作用的性质及其与另一种重要的钙结合蛋白钙调蛋白（calmodulin，CaM）的竞争，研究结果尚无定论。因此，需要使用低温电子显微镜（cryo-EM）技术在存在或不存在额外 CaM 的情况下，对 RyR 进行高分辨率研究。Weninger 等人的这项精巧工作通过各种实验证明了 S100A1 与 RyR1 之间的相互作用，并证实 S100A1 在亚微米 Ca 浓度下激活 RyR1，增加 RyR1 通道的开放概率。
