Chapter 4 : The Molecular Basis of K Channel Gating

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Until recently, electrophysiology served as an indirect window into one's understanding of channel gating and structure. A clearer picture of protein movements involved in gating has recently emerged from the merger of crystallographic and spectroscopic studies with functional analysis. These and other emerging results are discussed from the perspective that understanding the molecular process in details of gating helps explain how a wide variety of effectors can function to open or close a target channel, allowing for the large diversity of channels. A large helix opening may not be a requirement for channel gating as a small helix bend can allow K ions an adequate path for flow. The cytoplasmic gating ring of the channel is formed by an octamer of RCK domains. The mechanism of channel gating lies at the core of one's understanding of how channels respond to specific stimuli. Information extracted from functional, crystallographic, and spectroscopic studies of prokaryotic channels has revealed molecular details of how the inner helices and the selectivity filter are involved in channel gating. Focusing the gating forces at a consistent position along the ion conduction pathway allows channels to exist with a large diversity of regulatory domains but maintain a conserved core architecture necessary for efficient function.

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4

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Amino Acids
Membrane Protein
Escherichia coli
Ion Channels
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Image of Figure 1.
Figure 1.

Inner helix bending motion. (A) A single inner helix from the four known K channel structures (closed: KcsA, black; KirBac, dark gray; open: MthK, gray; KvAP, white) was aligned from the selectivity filter to the glycine hinge. The opposite KcsA inner helix is shown to provide the relative position of the bending helix within the tetramer. (B) A top view of the separation of inner transmembrane helices. (C) Cα-Cα?distances for residues along the inner helices of K channel structures provide an idea of the size of the ion conduction pathway. Major differences between open and closed channels occur after the glycine hinge.the rigidness of the whole helix has been shown by recent crystal structures to be broken at a glycine hinge point (equivalent to G99 in KcsA). Nevertheless, the specific details of the separation of the inner helices measured by EPR are a good representation of the movements involved in KcsA gating. In a complementary experiment using site-directed mass tagging of pore-lining residues in KcsA, an increase in cysteine residue accessibility to methanethiosulfonate reagents was observed at lower pH values ( ).

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4
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Image of Figure 2.
Figure 2.

MthK gating movements. Ligand-induced conformational changes in the cytoplasmic gating ring control the open state of MthK. A structural alignment (MthK-Ca, black; KtnBsu-nad, dark gray; Kch-empty, gray; KtnBsu-nadh, white) of the hinge between the RCK domain and the peripheral domain provides insight into the physical movements within the cytoplasmic domain dimer that occur in response to the release of ligand.

Citation: Ptak C, Liu Y, Perozo E. 2005. The Molecular Basis of K Channel Gating, p 69-81. In Kubalski A, Martinac B (ed), Bacterial Ion Channels and Their Eukaryotic Homologs. ASM Press, Washington, DC. doi: 10.1128/9781555816452.ch4
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