title: Length-dependent regulation of the Kv1.2 channel activation by its C-terminus.
abstract: The cytoplasmic C-terminus plays regulatory roles in the gating of many ion channels. However, lack of structural information on the C-terminus prevents the elucidation of how the C-terminal domain interacts with the gating machinery to exert its effects on the channel gating. In this report, we investigated the regulatory role of the C-terminus with functional study and structural modeling of a succession of C-terminal truncations of the Kv1.2 and Kv1.2(427)-KcsA(112-160) chimeric channels. Functional study demonstrated a length-dependent shift of the activation curves for the C-terminal truncations of the Kv1.2 channel. Structural modeling indicated that the C-terminus of one subunit could dynamically interact with the S4-S5 linker of a neighboring subunit and the probability of interaction was dependent on the length of the C-terminal truncated Kv1.2 channels. In contrast, no length-dependent shift of the activation curve and probability of interaction between C-terminus and the neighboring S4-S5 linker were observed for the truncations of the Kv1.2-KcsA chimeric channel, suggesting that the native C-terminus of the Kv1.2 channel is essential for the interaction. Furthermore, surface plasmon resonance measurements indicated that there is direct interaction between the C-terminal domain and the S4-S5 linker of the Kv1.2 channel. These results imply that the dynamic interaction of the C-terminus with the S4-S5 linker from a neighboring subunit of the Kv1.2 channel provides a mechanism for its C-terminus to regulate the channel activation.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhao
authors.forename: Aiping
authors.initials: A
authors.lastname: Wu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Bi
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.forename: Xian-En
authors.initials: XE
authors.lastname: Zhang
authors.forename: Taijiao
authors.initials: T
authors.lastname: Jiang
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D051663:Kv1.2 Potassium Channel / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D011487:Protein Conformation; D021122:Protein Subunits; D051381:Rats
chemical_list: D051663:Kv1.2 Potassium Channel; D021122:Protein Subunits