6U9T

Wild-type MthK pore in 50 mM K+

6U9T の概要

• エントリーDOI: 10.2210/pdb6u9t/pdb
• 分子名称: Calcium-gated potassium channel MthK, POTASSIUM ION, HEXANE-1,6-DIOL, ... (4 entities in total)
• 機能のキーワード: potassium ion channel mthk, transport protein
• 由来する生物種: Methanothermobacter thermautotrophicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9293.16

構造登録者

Posson, D.J.,Nimigean, C.M. (登録日: 2019-09-09, 公開日: 2020-11-04, 最終更新日: 2023-10-11)

主引用文献

Boiteux, C.,Posson, D.J.,Allen, T.W.,Nimigean, C.M.
Selectivity filter ion binding affinity determines inactivation in a potassium channel.
Proc.Natl.Acad.Sci.USA, 117:29968-29978, 2020

PubMed Abstract: Potassium channels can become nonconducting via inactivation at a gate inside the highly conserved selectivity filter (SF) region near the extracellular side of the membrane. In certain ligand-gated channels, such as BK channels and MthK, a Ca-activated K channel from , the SF has been proposed to play a role in opening and closing rather than inactivation, although the underlying conformational changes are unknown. Using X-ray crystallography, identical conductive MthK structures were obtained in wide-ranging K concentrations (6 to 150 mM), unlike KcsA, whose SF collapses at low permeant ion concentrations. Surprisingly, three of the SF's four binding sites remained almost fully occupied throughout this range, indicating high affinities (likely submillimolar), while only the central S2 site titrated, losing its ion at 6 mM, indicating low K affinity (∼50 mM). Molecular simulations showed that the MthK SF can also collapse in the absence of K, similar to KcsA, but that even a single K binding at any of the SF sites, except S4, can rescue the conductive state. The uneven titration across binding sites differs from KcsA, where SF sites display a uniform decrease in occupancy with K concentration, in the low millimolar range, leading to SF collapse. We found that ions were disfavored in MthK's S2 site due to weaker coordination by carbonyl groups, arising from different interactions with the pore helix and water behind the SF. We conclude that these differences in interactions endow the seemingly identical SFs of KcsA and MthK with strikingly different inactivating phenotypes.

PubMed: 33154158
DOI: 10.1073/pnas.2009624117

実験手法

X-RAY DIFFRACTION (1.55 Å)