Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane
Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane
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DOI：
10.1073/pnas.0507651102
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发表时间：
2005-10-25
影响因子：
11.1
通讯作者：
MacKinnon, R
中科院分区：
文献类型：
--
作者：
Lee, SY;Lee, A;MacKinnon, R
电压依赖的离子通道门打开，以响应细胞膜电压的变化。这种形式的门控允许动作电位的传播。我们提出了两种电压依赖性K+通道KvAP的结构，在含有单抗Fv片段的复合体中(3.9A)和在没有抗体片段的复合体中(8埃)。我们还研究了脂膜上具有二硫键交叉桥的KvAP。根据Kv1.2的晶体结构和KvAP上的EPR数据分析这些数据，我们得到以下结论：(1)KvAP与Kv1.2在结构上相似，但其电压传感器的取向略有不同：(H)单抗片段不是KvAP晶体结构中非天然构象的来源；(4)由于KvAP含有独立的松散附着的结构域，因此需要一个脂膜来保持它们的正确相对取向，并且(Iv)KvAP的模型与通过在蛋白质-脂质界面上移动一个含精氨酸的螺旋-转角-螺旋元件来进行电压传感的假设是一致的。
Voltage-dependent ion channels gate open in response to changes in cell membrane voltage. This form of gating permits the propagation of action potentials. We present two structures of the voltage-dependent K+ channel KvAP, in complex with monoclonal Fv fragments (3.9 A) and without antibody fragments (8 angstrom). We also studied KvAP with disulfide cross-bridges in lipid membranes. Analyzing these data in the context of the crystal structure of Kv1.2 and EPR data on KvAP we reach the following conclusions: (i) KvAP is similar in structure to Kv1.2 with a very modest difference in the orientation of its voltage sensor; (h) mAb fragments are not the source of non-native conformations of KvAP in crystal structures; (fit) because KvAP contains separate loosely adherent domains, a lipid membrane is required to maintain their correct relative orientations, and (iv) the model of KvAP is consistent with the proposal of voltage sensing through the movement of an arginine-containing helix-turn-helix element at the protein-lipid interface.