Robinson John M, Deutsch Carol
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neuron. 2005 Jan 20;45(2):223-32. doi: 10.1016/j.neuron.2004.12.043.
Acquisition of secondary, tertiary, and quaternary structure is critical to the fabrication, assembly, and function of ion channels, yet the relationship between these biogenic events remains unclear. We now address this issue in voltage-gated K(+) channels (Kv) for the T1 domain, an N-terminal Kv recognition domain that is responsible for subfamily-specific, efficient assembly of Kv subunits. This domain forms a 4-fold symmetric tetramer. We have identified residues along the axial T1-T1 interface that are critical for tertiary and quaternary structure, shown that mutations at one end of the axial T1 interface can perturb the crosslinking of an intersubunit cysteine pair at the other end, and demonstrated that tertiary folding and tetramerization of this Kv domain are coupled. A threshold level of tertiary folding is required for monomers to oligomerize. Coupling between tertiary and quaternary structure formation may be a common feature in the biogenesis of multimeric proteins.
二级、三级和四级结构的形成对于离子通道的制造、组装及功能至关重要，然而这些生物发生事件之间的关系仍不清楚。我们现在针对电压门控钾通道（Kv）的T1结构域来探讨这个问题，T1结构域是一个N端Kv识别结构域，负责Kv亚基的亚家族特异性高效组装。该结构域形成一个四重对称四聚体。我们已经确定了沿轴向T1-T1界面的残基对三级和四级结构至关重要，表明轴向T1界面一端的突变会干扰另一端亚基间半胱氨酸对的交联，并证明该Kv结构域的三级折叠和四聚化是耦合的。单体寡聚化需要一定阈值水平的三级折叠。三级和四级结构形成之间的耦合可能是多聚体蛋白质生物发生中的一个共同特征。
