FK506 结合蛋白 12 和 12.6（FKBP）作为心肌兰尼碱受体的调节剂：来自新的功能和结构知识的见解。
FK506-binding proteins 12 and 12.6 (FKBPs) as regulators of cardiac Ryanodine Receptors: Insights from new functional and structural knowledge.
机构信息
a Department of Physiology , School of Biomedical Sciences and HeartOtago, University of Otago , Dunedin, Otago , New Zealand.
出版信息
Channels (Austin). 2017 Sep 3;11(5):415-425. doi: 10.1080/19336950.2017.1344799. Epub 2017 Jun 21.
Abstract
Ryanodine Receptors (RyRs) are intracellular Ca channels that mediate Ca flux from the sarco(endo)plasmic reticulum in many cell types. The interaction of RyRs with FK506-binding proteins (FKBPs) has been proposed as an important regulatory mechanism, where the loss of this interaction leads to channel dysfunction. In the heart, phosphorylation of RyR has been suggested to disrupt the RyR-FKBP interaction promoting altered Ca signaling, heart failure and arrhythmias. However, the functional result of FKBP interaction with RyR and how this interaction is regulated remains highly controversial. Recently, high resolution structures of RyR have provided novel aspects to the ongoing debate. This review will discuss the most recent functional data in light of these new structures.
摘要
Ryanodine 受体（RyRs）是细胞内 Ca 通道，可介导多种细胞类型的肌浆网（内质网）内的 Ca 流。RyR 与 FK506 结合蛋白（FKBP）的相互作用被认为是一种重要的调节机制，这种相互作用的丧失会导致通道功能障碍。在心脏中，RyR 的磷酸化被认为会破坏 RyR-FKBP 相互作用，从而促进 Ca 信号的改变、心力衰竭和心律失常。然而，FKBP 与 RyR 的相互作用的功能结果以及这种相互作用如何被调节仍然存在很大争议。最近，RyR 的高分辨率结构为正在进行的争论提供了新的方面。本综述将根据这些新结构讨论最近的功能数据。
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