8EP0

Eag Kv channel with voltage sensor in the intermediate conformation

Summary for 8EP0

• Entry DOI: 10.2210/pdb8ep0/pdb
• Related: 8EOW 8EP1
• EMDB information: 28487 28494 28498
• Descriptor: Potassium voltage-gated channel subfamily H member 1, Calmodulin-1 (2 entities in total)
• Functional Keywords: voltage-gated potassium channel, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 8
• Total formula weight: 390910.81

Authors

Mandala, V.S.,MacKinnon, R. (deposition date: 2022-10-04, release date: 2022-11-16, Last modification date: 2025-05-28)

Primary citation

Mandala, V.S.,MacKinnon, R.
Voltage-sensor movements in the Eag Kv channel under an applied electric field.
Proc.Natl.Acad.Sci.USA, 119:e2214151119-e2214151119, 2022

PubMed Abstract: Voltage-dependent ion channels regulate the opening of their pores by sensing the membrane voltage. This process underlies the propagation of action potentials and other forms of electrical activity in cells. The voltage dependence of these channels is governed by the transmembrane displacement of the positive charged S4 helix within their voltage-sensor domains. We use cryo-electron microscopy to visualize this movement in the mammalian Eag voltage-dependent potassium channel in lipid membrane vesicles with a voltage difference across the membrane. Multiple structural configurations show that the applied electric field displaces S4 toward the cytoplasm by two helical turns, resulting in an extended interfacial helix near the inner membrane leaflet. The position of S4 in this down conformation is sterically incompatible with an open pore, thus explaining how movement of the voltage sensor at hyperpolarizing membrane voltages locks the pore shut in this kind of voltage-dependent K (K) channel. The structures solved in lipid bilayer vesicles detail the intricate interplay between K channels and membranes, from showing how arginines are stabilized deep within the membrane and near phospholipid headgroups, to demonstrating how the channel reshapes the inner leaflet of the membrane itself.

PubMed: 36331999
DOI: 10.1073/pnas.2214151119

Experimental method

ELECTRON MICROSCOPY (4.9 Å)