A structural link between inactivation and block of a K+ channel

被引：100

作者：

Ader, Christian ^{[2
]}

Schneider, Robert ^{[2
]}

Hornig, Soenke ^{[3
]}

Velisetty, Phanindra ^{[3
]}

Wilson, Erica M. ^{[1
]}

Lange, Adam ^{[2
]}

Giller, Karin ^{[2
]}

Ohmert, Iris ^{[3
]}

Martin-Eauclaire, Marie-France ^{[4
]}

Trauner, Dirk ^{[1
]}

Becker, Stefan ^{[2
]}

Pongs, Olaf ^{[3
]}

Baldus, Marc ^{[2
]}

机构：

[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[2] Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany

[3] Univ Hosp Hamburg Eppendorf, Ctr Mol Neurobiol, Inst Neural Signaltransduct, D-20251 Hamburg, Germany

[4] Univ Aix Marseille 2, Inst Jean Roche, CNRS, F-13916 Marseille 20, France

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2008年 / 15卷 / 06期

关键词：

D O I：

10.1038/nsmb.1430

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：

Gating the ion-permeation pathway in K+ channels requires conformational changes in activation and inactivation gates. Here we have investigated the structural alterations associated with pH-dependent inactivation gating of the KcsA-Kv1.3 K+ channel using solid-state NMR spectroscopy in direct reference to electrophysiological and pharmacological experiments. Transition of the KcsA-Kv1.3 K+ channel from a closed state at pH 7.5 to an inactivated state at pH 4.0 revealed distinct structural changes within the pore, correlated with activation-gate opening and inactivation-gate closing. In the inactivated K+ channel, the selectivity filter adopts a nonconductive structure that was also induced by binding of a pore-blocking tetraphenylporphyrin derivative. The results establish a structural link between inactivation and block of a K+ channel in a membrane setting.

引用

页码：605 / 612

页数：8

共 47 条

[1] Conformational dynamics of the KcsA potassium channel governs gating properties [J].

Baker, Kent A. ;

Tzitzilonis, Christos ;

Kwiatkowski, Witek ;

Choe, Senyon ;

Riek, Roland .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (11) :1089-1095

[2]

Baldus M, 1998, MOL PHYS, V95, P1197, DOI 10.1080/00268979809483251

[3] The action potential in mammalian central neurons [J].

Bean, Bruce P. .

NATURE REVIEWS NEUROSCIENCE, 2007, 8 (06) :451-465

[4] A gate in the selectivity filter of potassium channels [J].

Bernèche, S ;

Roux, BI .

STRUCTURE, 2005, 13 (04) :591-600

[5] FREQUENCY-SWITCHED PULSE SEQUENCES - HOMONUCLEAR DECOUPLING AND DILUTE SPIN NMR IN SOLIDS [J].

BIELECKI, A ;

KOLBERT, AC ;

LEVITT, MH .

CHEMICAL PHYSICS LETTERS, 1989, 155 (4-5) :341-346

[6] Detection of the opening of the bundle crossing in KcsA with fluorescence lifetime spectroscopy reveals the existence of two gates for ion conduction [J].

Blunck, Rikard ;

Cordero-Morales, Julio F. ;

Cuello, Luis G. ;

Perozo, Eduardo ;

Bezanilla, Francisco .

JOURNAL OF GENERAL PHYSIOLOGY, 2006, 128 (05) :569-581

[7] 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

[8] NMR study of the tetrameric KcsA potassium channel in detergent micelles [J].

Chill, JH ;

Louis, JM ;

Miller, C ;

Bax, A .

PROTEIN SCIENCE, 2006, 15 (04) :684-698

[9] Local and global structure of the monomeric subunit of the potassium channel KcsA probed by NMR [J].

Chill, Jordan H. ;

Louis, John M. ;

Delaglio, Frank ;

Bax, Ad .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2007, 1768 (12) :3260-3270

[10] Voltage-dependent gating at the KcsA selectivity filter [J].

Cordero-Morales, JF ;

Cuello, LG ;

Perozo, E .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2006, 13 (04) :319-322

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