Crystal Structure of a Voltage-gated K+ Channel Pore Module in a Closed State in Lipid Membranes

被引:20
作者
Santos, Jose S. [1 ]
Asmar-Rovira, Guillermo A. [2 ]
Han, Gye Won [2 ]
Liu, Wei [2 ]
Syeda, Ruhma [1 ]
Cherezov, Vadim [2 ]
Baker, Kent A. [2 ]
Stevens, Raymond C. [2 ]
Montal, Mauricio [1 ]
机构
[1] Univ Calif San Diego, Neurobiol Sect, Div Biol Sci, La Jolla, CA 92093 USA
[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
POTASSIUM-CHANNEL; SELECTIVITY FILTER; PROTEINS; RECEPTOR; MESOPHASES; RESOLUTION; SOFTWARE; COMPLEX; DESIGN; SYSTEM;
D O I
10.1074/jbc.M112.415091
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Voltage-gated K+ channels underlie the electrical excitability of cells. Each subunit of the functional tetramer consists of the tandem fusion of two modules, an N-terminal voltage-sensor and a C-terminal pore. To investigate how sensor coupling to the pore generates voltage-dependent channel opening, we solved the crystal structure and characterized the function of a voltage-gated K+ channel pore in a lipid membrane. The structure of a functional channel in a membrane environment at 3.1 angstrom resolution establishes an unprecedented connection between channel structure and function. The structure is unique in delineating an ion-occupied ready to conduct selectivity filter, a confined aqueous cavity, and a closed activation gate, embodying a dynamic entity trapped in an unstable closed state.
引用
收藏
页码:43063 / 43070
页数:8
相关论文
共 38 条
[1]   A model for 4-aminopyridine action on K channels: Similarities to tetraethylammonium ion action [J].
Armstrong, CM ;
Loboda, A .
BIOPHYSICAL JOURNAL, 2001, 81 (02) :895-904
[2]   INNER QUATERNARY AMMONIUM ION RECEPTOR IN POTASSIUM CHANNELS OF NODE OF RANVIER [J].
ARMSTRONG, CM ;
HILLE, B .
JOURNAL OF GENERAL PHYSIOLOGY, 1972, 59 (04) :388-+
[3]   Droplet interface bilayers [J].
Bayley, Hagan ;
Cronin, Brid ;
Heron, Andrew ;
Holden, Matthew A. ;
Hwang, William L. ;
Syeda, Ruhma ;
Thompson, James ;
Wallace, Mark .
MOLECULAR BIOSYSTEMS, 2008, 4 (12) :1191-1208
[4]   The voltage sensor in voltage-dependent ion channels [J].
Bezanilla, F .
PHYSIOLOGICAL REVIEWS, 2000, 80 (02) :555-592
[5]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[6]   Crystallizing membrane proteins using lipidic mesophases [J].
Caffrey, Martin ;
Cherezov, Vadim .
NATURE PROTOCOLS, 2009, 4 (05) :706-731
[7]   A robotic system for crystallizing membrane and soluble proteins in lipidic mesophases [J].
Cherezov, V ;
Peddi, A ;
Muthusubramaniam, L ;
Zheng, YF ;
Caffrey, M .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2004, 60 :1795-1807
[8]   Rastering strategy for screening and centring of microcrystal samples of human membrane proteins with a sub-10 μm size X-ray synchrotron beam [J].
Cherezov, Vadim ;
Hanson, Michael A. ;
Griffith, Mark T. ;
Hilgart, Mark C. ;
Sanishvili, Ruslan ;
Nagarajan, Venugopalan ;
Stepanov, Sergey ;
Fischetti, Robert F. ;
Kuhn, Peter ;
Stevens, Raymond C. .
JOURNAL OF THE ROYAL SOCIETY INTERFACE, 2009, 6 :S587-S597
[9]   Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel [J].
Clayton, Gina M. ;
Altieri, Steve ;
Heginbotham, Lise ;
Unger, Vinzenz M. ;
Morais-Cabral, Joao H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (05) :1511-1515
[10]   Molecular determinants of gating at the potassium-channel selectivity filter [J].
Cordero-Morales, JF ;
Cuello, LG ;
Zhao, YX ;
Jogini, V ;
Cortes, DM ;
Roux, B ;
Perozo, E .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (04) :311-318