MOLECULAR-MODEL OF THE ACTION-POTENTIAL SODIUM-CHANNEL
MOLECULAR-MODEL OF THE ACTION-POTENTIAL SODIUM-CHANNEL
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DOI：
10.1073/pnas.83.2.508
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发表时间：
1986-01-01
影响因子：
11.1
通讯作者：
SEETHARAMULU, P
中科院分区：
文献类型：
--
作者：
GUY, HR;SEETHARAMULU, P
钠通道跨膜片段的二级和三级结构模型是根据最近确定的电电鱼一级序列开发的。该模型有四个同源域，每个域有八个同源跨膜片段，S1 到 S8。每个结构域包含三个相对非极性的片段(S1、S2和S3)和两个非常非极性的片段(S5和S8)，所有这些都被假定为跨膜α-螺旋。 S4 片段每隔三个残基就有一个带正电的残基，主要是精氨酸。模型通道衬里由四个S4跨膜α-螺旋和四个带负电的S7节段形成。假定S7片段在三个结构域中是短的、部分跨膜的两亲性α螺旋，在最后一个结构域中是β链。 S7片段之前是短非极性片段(S6)，假定在三个结构域中是α-螺旋，在最后一个结构域中是β-链。 S4 带正电的侧链与 S7 带负电的侧链以及 S1 和 S3 末端附近形成盐桥。假定的细胞外片段包含 10 个潜在 N-糖基化位点中的 5 个，将 S5 连接到 S6。通道激活可能涉及“螺旋”机制，其中 S4 螺旋在移向细胞外表面时绕其轴旋转。
Secondary and tertiary structural models of sodium channel transmembrane segments were developed from its recently determined primary sequence in Electrophorus electricus. The model has four homologous domains, and each domain has eight homologous transmembrane segments, S1 through S8. Each domain contains three relatively apolar segments (S1, S2, and S3) and two very apolar segments (S5 and S8), all postulated to be transmembrane .alpha.-helices. S4 segments have positively charged residues, mainly arginines, at every third residue. The model channel lining is formed by four S4 transmembrane .alpha.-helices and four negatively charged S7 segments. S7 segments are postulated to be short, partially transmembrane amphipathic .alpha.-helices in three domains and a .beta.-strand in the last domain. S7 segments are preceeded by short apolar segments (S6) postulated to be .alpha.-helices in three domains and a .beta.-strand in the last domain. Positively charged side chains of S4 form salt bridges with negatively charged side chains of S7 and near the ends of S1 and S3. Putative extracellular segments that contain 5 of the 10 potential N-glycosylation sites link S5 to S6. Channel activation may involve a ''helical screw'' mechanism in which S4 helices rotate around their axes as they move toward the extracellular surface.