Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification
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DOI：
10.1038/nn1411
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发表时间：
2005-03-01
影响因子：
25
通讯作者：
Choe, S
中科院分区：
文献类型：
--
作者：
Pegan, S;Arrabit, C;Choe, S
内向整流钾通道的N-和C-末端胞质结构域通过与细胞质中的小分子和蛋白质配体的多种相互作用控制离子渗透途径。在不存在PIP 2的情况下，Kir2.1（Kir2.1（L））和G蛋白敏感性Kir3.1（Kir3.1（S））通道的细胞质结构域的两种新晶体结构显示了被四个细胞质环封闭的细胞质离子渗透途径，所述细胞质环形成围绕中心孔（G环）的环带。Kir2.1（L）和Kir3.1（S）的面向孔的G环的显著柔性表明可能作为细胞质和跨膜孔之间的扩散屏障的作用。与此相一致的是，G环的突变破坏了门控或内向整流。结构比较显示Kir2.1（L）细胞质孔远端的二天冬氨酸簇对调节内向整流很重要。总之，这些结果表明Kir通道的胞质结构域经历结构变化以调节门控和内向整流。
N- and C-terminal cytoplasmic domains of inwardly rectifying K (Kir) channels control the ion-permeation pathway through diverse interactions with small molecules and protein ligands in the cytoplasm. Two new crystal structures of the cytoplasmic domains of Kir2.1 (Kir2.1(L)) and the G protein-sensitive Kir3.1 (Kir3.1(S)) channels in the absence of PIP2 show the cytoplasmic ion-permeation pathways occluded by four cytoplasmic loops that form a girdle around the central pore (G-loop). Significant flexibility of the pore-facing G-loop of Kir2.1(L) and Kir3.1(S) suggests a possible role as a diffusion barrier between cytoplasmic and transmembrane pores. Consistent with this, mutations of the G-loop disrupted gating or inward rectification. Structural comparison shows a di-aspartate cluster on the distal end of the cytoplasmic pore of Kir2.1(L) that is important for modulating inward rectification. Taken together, these results suggest the cytoplasmic domains of Kir channels undergo structural changes to modulate gating and inward rectification.