Topology of a functionally important region of the cardiac Na+/Ca2+ exchanger
Topology of a functionally important region of the cardiac Na+/Ca2+ exchanger
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DOI：
10.1074/jbc.273.2.778
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发表时间：
1998-01-09
影响因子：
4.8
通讯作者：
Philipson, KD
中科院分区：
文献类型：
--
作者：
Doering, AE;Nicoll, DA;Philipson, KD
心脏 Na+/Ca2+ 交换器 NCX1 已被建模为由 11 个跨膜片段和一个大的细胞质环（环 f）组成，半胱氨酸诱变和巯基修饰实验表明，连接跨膜片段 1 和 2 的环（环 b）位于膜的细胞质侧，如先前建模的那样。 b 环中的天冬酰胺 101 突变为半胱氨酸 (N101C)，使交换器对细胞质 Na+ 和 Ca2+ 的调节不敏感。残基苏氨酸 103（T103C 或 T103V）附近的突变增加了交换器对细胞质 Na+ 的表观亲和力，并且还产生显着的 Li+ 转运能力。证据表明，细胞质环 b 和跨膜片段 2 界面处的区域对于 Na+ 转运和二级调节很重要，因此，该区域可能构成所形成的离子易位途径之间联系的一部分。 由先前定位于环 f 的跨膜片段和调节位点组成。
The cardiac Na+/Ca2+ exchanger, NCX1, has been modeled to consist of 11 transmembrane segments and a large cytoplasmic loop (loop f), Cysteine mutagenesis and sulfhydryl modification experiments demonstrate that the loop connecting transmembrane segments 1 and 2 (loop b) is located on the cytoplasmic side of the membrane, as previously modeled. A mutation in loop b, asparagine 101 to cysteine (N101C), renders the exchanger insensitive to regulation by cytoplasmic Na+ and Ca2+. Nearby mutations at residue threonine 103 (T103C or T103V) increase the apparent affinity of the exchanger for cytoplasmic Na+ and also produce a significant Li+ transport capacity, The evidence suggests that the region at the interface of cytoplasmic loop b and transmembrane segment 2 is important in Na+ transport and also in secondary regulation, Thus, this region may form part of the link between the ion translocation pathway formed by the transmembrane segments and regulatory sites that have previously been localized to loop f.