The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel

被引：70

作者：

Peters, Christian J. ^{[1
,2
,3
]}

Gilchrist, John M. ^{[1
,2
,3
]}

Tien, Jason ^{[1
,2
,3
]}

Bethel, Neville P. ^{[4
,5
]}

Qi, Lijun ^{[1
,2
,3
]}

Chen, Tingxu ^{[1
,2
,3
]}

Wang, Lynn ^{[1
,2
,3
]}

Jan, Yuh Nung ^{[1
,2
,3
,6
]}

Grabe, Michael ^{[4
,5
]}

Jan, Lily Y. ^{[1
,2
,3
,6
]}

机构：

[1] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94158 USA

[4] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA

[5] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA

[6] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA

来源：

NEURON | 2018年 / 97卷 / 05期

关键词：

SHAKER POTASSIUM CHANNEL; ADDITIVE FORCE-FIELD; SMOOTH-MUSCLE; INDEPENDENT ACTIVATION; CRYO-EM; PROTEIN; EXPRESSION; BLOCKER; SCRAMBLASE; MECHANISM;

D O I：

10.1016/j.neuron.2018.01.048

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions. To understand how CaCC regulates neuronal signaling and how CaCC is, in turn, modulated by neuronal activity, we examined the molecular basis of CaCC gating. Here, we report that voltage modulation of TMEM16A-CaCC involves voltage-dependent occupancy of calcium- and anion-binding site(s) within the membrane electric field as well as a voltage-dependent conformational change intrinsic to the channel protein. These gating modalities all critically depend on the sixth transmembrane segment.

引用

页码：1063 / +

页数：19

共 42 条

[21] CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field [J].

Lee, Jumin ;

Cheng, Xi ;

Swails, Jason M. ;

Yeom, Min Sun ;

Eastman, Peter K. ;

Lemkul, Justin A. ;

Wei, Shuai ;

Buckner, Joshua ;

Jeong, Jong Cheol ;

Qi, Yifei ;

Jo, Sunhwan ;

Pande, Vijay S. ;

Case, David A. ;

Brooks, Charles L., III ;

MacKerell, Alexander D., Jr. ;

Klauda, Jeffery B. ;

Im, Wonpil .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2016, 12 (01) :405-413

[22] Independent activation of ion conduction pores in the double-barreled calcium-activated chloride channel TMEM16A [J].

Lim, Novandy K. ;

Lam, Andy K. M. ;

Dutzler, Raimund .

JOURNAL OF GENERAL PHYSIOLOGY, 2016, 148 (05) :375-392

[23] TMEM16A/Anoctamin 1 protein mediates calcium-activated chloride currents in pulmonary arterial smooth muscle cells [J].

Manoury, Boris ;

Tamuleviciute, Aiste ;

Tammaro, Paolo .

JOURNAL OF PHYSIOLOGY-LONDON, 2010, 588 (13) :2305-2314

[24] TMEM16A Inhibitors Reveal TMEM16A as a Minor Component of Calcium-activated Chloride Channel Conductance in Airway and Intestinal Epithelial Cells [J].

Namkung, Wan ;

Phuan, Puay-Wah ;

Verkman, A. S. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (03) :2365-2374

[25] Activation and Inhibition of TMEM16A Calcium-Activated Chloride Channels [J].

Ni, Yu-Li ;

Kuan, Ai-Seon ;

Chen, Tsung-Yu .

PLOS ONE, 2014, 9 (01)

[26] MONNA, a Potent and Selective Blocker for Transmembrane Protein with Unknown Function 16/Anoctamin-1 [J].

Oh, Soo-Jin ;

Hwang, Seok Jin ;

Jung, Jonghoon ;

Yu, Kuai ;

Kim, Jeongyeon ;

Choi, Jung Yoon ;

Hartzell, H. Criss ;

Roh, Eun Joo ;

Lee, C. Justin .

MOLECULAR PHARMACOLOGY, 2013, 84 (05) :726-735

[27] Activation mechanism of the calcium-activated chloride channel TMEM16A revealed by cryo-EM [J].

Paulino, Cristina ;

Kalienkova, Valeria ;

Lam, Andy K. M. ;

Neldner, Yvonne ;

Dutzler, Raimund .

NATURE, 2017, 552 (7685) :421-+

[28] Permeant anions control gating of calcium-dependent chloride channels [J].

Perez-Cornejo, P ;

De Santiago, JA ;

Arreola, J .

JOURNAL OF MEMBRANE BIOLOGY, 2004, 198 (03) :125-133

[29] Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels [J].

Peters, Christian J. ;

Yu, Haibo ;

Tien, Jason ;

Jan, Yuh Nung ;

Li, Min ;

Jan, Lily Yeh .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (11) :3547-3552

[30] COMPARATIVE PROTEIN MODELING BY SATISFACTION OF SPATIAL RESTRAINTS [J].

SALI, A ;

BLUNDELL, TL .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (03) :779-815

← 1 2 3 4 5 →