6W7B

K2P2.1 (TREK-1), 0 mM K+

Summary for 6W7B

• Entry DOI: 10.2210/pdb6w7b/pdb
• Descriptor: Potassium channel subfamily K member 2, CADMIUM ION, DODECANE, ... (7 entities in total)
• Functional Keywords: ion channel, k2p, trek1, trek-1, metal transport
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 70070.98

Authors

Lolicato, M.,Minor, D.L. (deposition date: 2020-03-19, release date: 2021-01-27, Last modification date: 2024-11-13)

Primary citation

Lolicato, M.,Natale, A.M.,Abderemane-Ali, F.,Crottes, D.,Capponi, S.,Duman, R.,Wagner, A.,Rosenberg, J.M.,Grabe, M.,Minor Jr., D.L.
K 2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.
Sci Adv, 6:-, 2020

PubMed Abstract: K potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric Ks is unknown. Here, combining K2.1 (TREK-1) x-ray crystallography in different potassium concentrations, potassium anomalous scattering, molecular dynamics, and electrophysiology, we uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K C-type gating. These asymmetric order-disorder transitions, enabled by the K heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K SF2-M4 loop and conserved "M3 glutamate network," and are suppressed by the K C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K channel modulator development.

PubMed: 33127683
DOI: 10.1126/sciadv.abc9174

Experimental method

X-RAY DIFFRACTION (3.88 Å)