Interaction sites between the Slo1 pore and the NH2 terminus of the beta2 subunit, probed with a three-residue sensor.

Slo1 孔和 β 2 亚基的 NH2 末端之间的相互作用位点 ，用三残留传感器探测。

• 发表时间: Jun 2007 15
• 来源期刊: J Biol Chem
• DOI: 10.1074/jbc.M607063200
• PMID: 17430898
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 生物
• 作者列表: Li H,Yao J,Tong X,Guo Z,Wu Y,Sun L,Pan N,Wu H,Xu T,Ding J

Mesh: Amino Acid Sequence; Animals; Binding Sites; DNA Mutational Analysis; Humans; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / chemistry genetics metabolism; Large-Conductance Calcium-Activated Potassium Channel beta Subunits / chemistry genetics metabolism; Mice; Models, Molecular; Molecular Sequence Data; Molecular Structure; Mutagenesis, Site-Directed; Patch-Clamp Techniques; Protein Structure, Tertiary; Sequence Alignment; Xenopus laevis

Abstract

Calcium- and voltage-gated (BK) K(+) channels encoded by Slo1 play an essential role in nervous systems. Although it shares many common features with voltage-dependent K(V) channels, the BK channel exhibits differences in gating and inactivation. Using a mutant in which FWI replaces three residues (FIW) in the NH(2) terminus of wild-type beta2-subunits, in conjunction with alanine-scanning mutagenesis of the Slo1 S6 segment, we identify that the NH(2) terminus of beta2-subunits interacts with the residues near the cytosolic superficial mouth of BK channels during inactivation. The cytosolic blockers did not share the sites with NH(2) terminus of beta2-subunits. A novel blocking-inactivating scheme was proposed to account for the observed non-competition inactivation. Our results also suggest that the residue Ile-323 plays a dual role in interacting with the NH(2) terminus of beta2-subunits and modulating the gating of BK channels.