Structure acquisition of the T1 domain of Kv1.3 during biogenesis
Structure acquisition of the T1 domain of Kv1.3 during biogenesis
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DOI：
10.1016/j.neuron.2004.09.011
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发表时间：
2004-10-14
期刊：
影响因子：
16.2
通讯作者：
Deutsch, C
中科院分区：
文献类型：
--
作者：
Kosolapov, A;Tu, LW;Deutsch, C
电压门控K+（Kv）通道亚基的T1识别结构域形成四聚体，并获得三级结构，同时仍然连接到它们各自的核糖体。在这里，我们问什么时候和在哪个区室获得二级和三级结构。我们回答这个问题，使用生物中间体和最近开发的折叠和可访问性测定，以评估核糖体内外的新生KV肽的状态。与成熟结构中的螺旋性区域相对应的紧凑结构（可能是螺旋的）已经在核糖体隧道内的新生蛋白质中表现出来。T1结构域仅在从核糖体出口通道出现并完全合成T1-S1接头后获得三级结构。这些测量的核糖体隧道内的离子通道折叠及其出口端口承担蛋白质折叠的基本原则，并铺平了道路，了解蛋白质错误折叠的分子基础，通道病的根本原因。
The T1 recognition domains of voltage-gated K+ (Kv) channel subunits form tetramers and acquire tertiary structure while still attached to their individual ribosomes. Here we ask when and in which compartment secondary and tertiary structures are acquired. We answer this question using biogenic intermediates and recently developed folding and accessibility assays to evaluate the status of the nascent Kv peptide both inside and outside of the ribosome. A compact structure (likely helical) that corresponds to a region of helicity in the mature structure is already manifest in the nascent protein within the ribosomal tunnel. The T1 domain acquires tertiary structure only after emerging from the ribosomal exit tunnel and complete synthesis of the T1-S1 linker. These measurements of ion channel folding within the ribosomal tunnel and its exit port bear on basic principles of protein folding and pave the way for understanding the molecular basis of protein misfolding, a fundamental cause of channelopathies.