A Basic Cluster Determines Topology of the Cytoplasmic M3-M4 Loop of the Glycine Receptor α1 Subunit*
A Basic Cluster Determines Topology of the Cytoplasmic M3-M4 Loop of the Glycine Receptor α1 Subunit*
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基本簇决定甘氨酸受体 α1 亚基的细胞质 M3-M4 环的拓扑结构*
DOI：
10.1074/jbc.m213077200
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
G. Schmalzing
中科院分区：
文献类型：
--
作者：
S. Sadtler;B. Laube;Alhassan Lashub;A. Nicke;H. Betz;G. Schmalzing
抑制性甘氨酸受体是神经递质受体的配体门控离子通道超家族的成员，其由各自具有四个跨膜区段（M1-M4）的同源亚基组成。在这里，我们证明了甘氨酸受体α1亚基的正确拓扑结构关键取决于位于M3 C-末端后的大胞质环（命名为M3-M4环）中的碱性簇RFRRKRR内的6个带正电荷的残基。该簇的一个或多个电荷的中和，而不是M3-M4环中的其他带电残基的中和，导致异常易位到M3-M4环的内质网腔中。然而，当位于连接M2和M3的胞外域中的三个碱性电荷中的两个被中和时，除了碱性簇的两个电荷之外，M3-M4环的内质网处置被阻止。我们的结论是，需要高密度的碱性残基C-末端M3的存在下，带正电荷的残基在M2-M3胞外域，否则损害正确的膜整合的M3节段进行补偿。
The inhibitory glycine receptor is a member of the ligand-gated ion channel superfamily of neurotransmitter receptors, which are composed of homologous subunits with four transmembrane segments (M1-M4), each. Here, we demonstrate that the correct topology of the glycine receptor α1 subunit depends critically on six positively charged residues within a basic cluster, RFRRKRR, located in the large cytoplasmic loop (designated M3-M4 loop) following the C-terminal end of M3. Neutralization of one or more charges of this cluster, but not of other charged residues in the M3-M4 loop, led to an aberrant translocation into the endoplasmic reticulum lumen of the M3-M4 loop. However, when two of the three basic charges located in the ectodomain linking M2 and M3 were neutralized, in addition to two charges of the basic cluster, endoplasmic reticulum disposition of the M3-M4 loop was prevented. We conclude that a high density of basic residues C-terminal to M3 is required to compensate for the presence of positively charged residues in the M2-M3 ectodomain, which otherwise impair correct membrane integration of the M3 segment.
DOI：
10.1073/pnas.86.15.5786
发表时间：
1989-08-01
影响因子：
11.1
作者：
HARTMANN, E;RAPOPORT, TA;LODISH, HF
通讯作者：
LODISH, HF