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

文献类型：期刊论文

作者Derebe, Mehabaw G.3; Zeng, Weizhong2,3; Li, Yang1; Alam, Amer4; Jiang, Youxing2,3
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2011-01-11
卷号108期号:2页码:592-597
ISSN号0027-8424
DOI10.1073/pnas.1013643108
文献子类Article
英文摘要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.
WOS关键词GMP-ACTIVATED CHANNEL ; DIVALENT-CATION SELECTIVITY ; OUTER SEGMENT MEMBRANE ; MOLECULAR DETERMINANTS ; TIGER SALAMANDER ; EXCISED PATCHES ; RETINAL RODS ; NAK CHANNEL ; CGMP ; PHOTORECEPTORS
资助项目US Department of Energy, Office of Energy Research[00000000] ; The Howard Hughes Medical Institute[00000000] ; National Institute of Health[GM079179] ; The David and Lucile Packard Foundation[00000000] ; National Institutes of Health[5 F31 GM07703]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000286097700033
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/278625]  
专题药理学第二研究室
通讯作者Jiang, Youxing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
2.Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA;
3.Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA;
4.ETH, Inst Mol Biol & Biophys, HPK D11, CH-8093 Zurich, Switzerland
推荐引用方式
GB/T 7714		 Derebe, Mehabaw G.,Zeng, Weizhong,Li, Yang,et al. Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2011,108(2):592-597.
APA Derebe, Mehabaw G.,Zeng, Weizhong,Li, Yang,Alam, Amer,&Jiang, Youxing.(2011).Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,108(2),592-597.
MLA Derebe, Mehabaw G.,et al."Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108.2(2011):592-597.

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来源：上海药物研究所

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