Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore

Mehabaw G. Derebe, Weizhong Zeng, Yang Li, Amer Alam, Youxing Jiang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Cyclic nucleotide-gated (CNG) channels play an essential role in the visual and olfactory sensory systems and are ubiquitous in eukaryotes. Details of their underlying ion selectivity properties are still not fully understood and are a matter of debate in the absence of high-resolution structures. To reveal the structural mechanism of ion selectivity in CNG channels, particularly their Ca2+ blockage property, we engineered a set of mimics of CNG channel pores for both structural and functional analysis. The mimics faithfully represent the CNG channels they are modeled after, permeate Na+ and K+ equally well, and exhibit the same Ca2+ blockage and permeation properties. Their high-resolution structures reveal a hitherto unseen selectivity filter architecture comprising three contiguous ion binding sites in which Na+ and K+ bind with different ion-ligand geometries. Our structural analysis reveals that the conserved acidic residue in the filter is essential for Ca2+ binding but not through direct ion chelation as in the currently accepted view. Furthermore, structural insight from our CNG mimics allows us to pinpoint equivalent interactions in CNG channels through structure-based mutagenesis that have previously not been predicted using NaK or K+ channel models.

Original languageEnglish (US)
Pages (from-to)592-597
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number2
DOIs
StatePublished - Jan 11 2011

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Cyclic Nucleotide-Gated Cation Channels
Ions
Cyclic Nucleotides
Eukaryota
Mutagenesis
Binding Sites
Ligands

ASJC Scopus subject areas

  • General

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Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore. / Derebe, Mehabaw G.; Zeng, Weizhong; Li, Yang; Alam, Amer; Jiang, Youxing.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 2, 11.01.2011, p. 592-597.

Research output: Contribution to journalArticle

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