Magidovich Elhanan, Fleishman Sarel J, Yifrach Ofer
Department of Life Sciences and the Zlotowski Center for Neurosciences, Ben Gurion University of the Negev Beer Sheva, Israel.
Bioinformatics. 2006 Jul 1;22(13):1546-50. doi: 10.1093/bioinformatics/btl137. Epub 2006 Apr 6.
Membrane-embedded voltage-activated potassium channels (Kv) bind intracellular scaffold proteins, such as the Post Synaptic Density 95 (PSD-95) protein, using a conserved PDZ-binding motif located at the channels' C-terminal tip. This interaction underlies Kv-channel clustering, and is important for the proper assembly and functioning of the synapse. Here we demonstrate that the C-terminal segments of Kv channels adjacent to the PDZ-binding motif are intrinsically disordered. Phylogenetic analysis of the Kv channel family reveals a cluster of channel sequences belonging to three out of the four main channel families, for which an association is demonstrated between the presence of the consensus terminal PDZ-binding motif and the intrinsically disordered nature of the immediately adjacent C-terminal segment. Our observations, combined with a structural analogy to the N-terminal intra-molecular ball-and-chain mechanism for Kv channel inactivation, suggest that the C-terminal disordered segments of these channel families encode an inter-molecular fishing rod-like mechanism for K(+) channel binding to scaffold proteins.
膜嵌入电压激活钾通道（Kv）利用位于通道C末端的保守PDZ结合基序，与细胞内支架蛋白（如突触后致密蛋白95（PSD - 95））结合。这种相互作用是Kv通道聚集的基础，对突触的正确组装和功能很重要。在这里，我们证明了与PDZ结合基序相邻的Kv通道C末端片段本质上是无序的。Kv通道家族的系统发育分析揭示了属于四个主要通道家族中三个家族的一组通道序列，对于这些序列，已证明共有末端PDZ结合基序的存在与紧邻的C末端片段的本质无序性质之间存在关联。我们的观察结果，结合与Kv通道失活的N末端分子内球链机制的结构类比，表明这些通道家族的C末端无序片段编码了一种分子间钓竿样机制，用于K(+)通道与支架蛋白结合。
