The Intracellular Loop of the Na+/Ca2+ Exchanger Contains an “Awareness Ribbon”-Shaped Two-Helix Bundle Domain,Biochemistry

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The Intracellular Loop of the Na+/Ca2+ Exchanger Contains an “Awareness Ribbon”-Shaped Two-Helix Bundle Domain
Biochemistry ( IF 2.9 ) Pub Date : 2018-06-13 00:00:00 , DOI: 10.1021/acs.biochem.8b00300
Jiaqi Yuan ₁ , Chunhua Yuan ₂ , Mouzhe Xie ₁ , Lei Yu ₁ , Lei Bruschweiler-Li ₂ , Rafael Brüschweiler _{1,

2,

3}

Affiliation

The Na⁺/Ca²⁺ exchanger (NCX) is a ubiquitous single-chain membrane protein that plays a major role in regulating the intracellular Ca²⁺ homeostasis by the counter transport of Na⁺ and Ca²⁺ across the cell membrane. Other than its prokaryotic counterpart, which contains only the transmembrane domain and is self-sufficient as an active ion transporter, the eukaryotic NCX protein possesses in addition a large intracellular loop that senses intracellular calcium signals and controls the activation of ion transport across the membrane. This provides a necessary layer of regulation for the more complex function of eukaryotic cells. The Ca²⁺ sensor in the intracellular loop is known as the Ca²⁺-binding domain (CBD12). However, how the signaling of the allosteric intracellular Ca²⁺ binding propagates and results in transmembrane ion transportation still lacks a detailed explanation. Further structural and dynamics characterization of the intracellular loop flanking both sides of CBD12 is therefore imperative. Here, we report the identification and characterization of another structured domain that is N-terminal to CBD12 in the intracellular loop using solution nuclear magnetic resonance (NMR) spectroscopy. The atomistic structure of this domain reveals that two tandem long α-helices, connected by a short linker, form a stable crossover two-helix bundle (THB), resembling an “awareness ribbon”. Considering the highly conserved amino acid sequence of the THB domain, the detailed structural and dynamics properties of the THB domain will be common among NCXs from different species and will contribute toward the understanding of the regulatory mechanism of eukaryotic Na⁺/Ca²⁺ exchangers.

中文翻译：

Na ⁺ / Ca ²⁺交换子的细胞内环包含“意识带”形的两螺旋束域

Na ⁺ / Ca ²⁺交换子（NCX）是一种普遍存在的单链膜蛋白，通过Na ⁺和Ca ²⁺跨细胞膜的反向转运，在调节细胞内Ca ²⁺稳态中起主要作用。除了其原核对应物（仅包含跨膜结构域并且作为活性离子转运蛋白是自给自足的）以外，真核NCX蛋白还具有一个大的细胞内环，该环可感知细胞内钙信号并控制跨膜的离子转运的激活。这为真核细胞的更复杂功能提供了必要的调节层。Ca ²⁺细胞内环中的传感器被称为Ca ²⁺结合域（CBD12）。然而，变构细胞内Ca ²⁺的信号转导结合传播并导致跨膜离子运输仍然缺乏详细的解释。因此，必须对CBD12两侧的胞内环进行进一步的结构和动力学表征。在这里，我们报告使用溶液核磁共振（NMR）光谱在细胞内环中CBD12 N端的另一个结构域的鉴定和表征。该域的原子结构表明，两个串联的长α螺旋通过短连接子连接，形成稳定的交叉两螺旋束（THB），类似于“意识带”。考虑到THB结构域的高度保守的氨基酸序列，⁺ / Ca ²⁺交换器。

更新日期：2018-06-13

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