Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating

Zhong Ping Sun; Myles H. Akabas; Evan H. Goulding; Arthur Karlin; Steven A. Siegelbaum

doi:10.1016/S0896-6273(00)80031-8

Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating

Zhong Ping Sun^*, Myles H. Akabas, Evan H. Goulding, Arthur Karlin, Steven A. Siegelbaum

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

106 Scopus citations

Abstract

In voltage-gated ion channels and in the homologous cyclic nucleotide- gated (CNG) channels, the loop between the S5 and S6 transmembrane segments (P region) is thought to form the lining of the pore. To investigate the structure and the role in gating of the P region of the bovine retinal CNG channel, we determined the accessibility of 11 cysteine-substituted P region residues to small, charged sulfhydryl reagents applied to the inside and outside of membrane patches in the open and closed states of the channel. The results suggest that the P region forms a loop that extends toward the central axis of the channel, analogous to the L3 loop of bacterial porin channels. Furthermore, the P region, in addition to forming the ion selectivity filter, functions as the channel gate, the structure of which changes when the channel opens.

Original language	English (US)
Pages (from-to)	141-149
Number of pages	9
Journal	Neuron
Volume	16
Issue number	1
DOIs	https://doi.org/10.1016/S0896-6273(00)80031-8
State	Published - Jan 1996

Funding

We thank Drs. Gareth Tibbs and Juan Pascual for their comments on the manuscript, Huan Yao and John Riley for technical assistance, and Eric Odell for artwork. This work was supported in part by research grants from the National Institutes of Health (NS07065 to A. K. and NS30808 to M. H. A.), the American Heart Association (M. H. A.), the McKnight Endowment for Neuroscience (A. K.), and the Muscular Dystrophy Association (A. K.). M. H. A. is the recipient of a Klingenstein Award in the Neurosciences and is an Established Scientist of the New York Heart Association. S. A. S. is an Investigator of the Howard Hughes Medical Institute.

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(00)80031-8

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title = "Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating",

abstract = "In voltage-gated ion channels and in the homologous cyclic nucleotide- gated (CNG) channels, the loop between the S5 and S6 transmembrane segments (P region) is thought to form the lining of the pore. To investigate the structure and the role in gating of the P region of the bovine retinal CNG channel, we determined the accessibility of 11 cysteine-substituted P region residues to small, charged sulfhydryl reagents applied to the inside and outside of membrane patches in the open and closed states of the channel. The results suggest that the P region forms a loop that extends toward the central axis of the channel, analogous to the L3 loop of bacterial porin channels. Furthermore, the P region, in addition to forming the ion selectivity filter, functions as the channel gate, the structure of which changes when the channel opens.",

author = "Sun, {Zhong Ping} and Akabas, {Myles H.} and Goulding, {Evan H.} and Arthur Karlin and Siegelbaum, {Steven A.}",

note = "Funding Information: We thank Drs. Gareth Tibbs and Juan Pascual for their comments on the manuscript, Huan Yao and John Riley for technical assistance, and Eric Odell for artwork. This work was supported in part by research grants from the National Institutes of Health (NS07065 to A. K. and NS30808 to M. H. A.), the American Heart Association (M. H. A.), the McKnight Endowment for Neuroscience (A. K.), and the Muscular Dystrophy Association (A. K.). M. H. A. is the recipient of a Klingenstein Award in the Neurosciences and is an Established Scientist of the New York Heart Association. S. A. S. is an Investigator of the Howard Hughes Medical Institute. ",

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AU - Siegelbaum, Steven A.

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AB - In voltage-gated ion channels and in the homologous cyclic nucleotide- gated (CNG) channels, the loop between the S5 and S6 transmembrane segments (P region) is thought to form the lining of the pore. To investigate the structure and the role in gating of the P region of the bovine retinal CNG channel, we determined the accessibility of 11 cysteine-substituted P region residues to small, charged sulfhydryl reagents applied to the inside and outside of membrane patches in the open and closed states of the channel. The results suggest that the P region forms a loop that extends toward the central axis of the channel, analogous to the L3 loop of bacterial porin channels. Furthermore, the P region, in addition to forming the ion selectivity filter, functions as the channel gate, the structure of which changes when the channel opens.

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Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating

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