A Bivalent Tarantula Toxin Activates the Capsaicin Receptor, TRPV1, by Targeting the Outer Pore Domain

被引：261

作者：

Bohlen, Christopher J. ^{[1
]}

Priel, Avi ^{[1
]}

Zhou, Sharleen ^{[2
]}

King, David ^{[2
]}

Siemens, Jan ^{[1
]}

Julius, David ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA

[2] Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Berkeley, CA 94720 USA

来源：

CELL | 2010年 / 141卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GATING MODIFIER TOXINS; SPIDER SELENOCOSMIA-HUWENA; DEPENDENT K+ CHANNELS; VOLTAGE-SENSOR; POTASSIUM CHANNEL; ION-CHANNEL; MOLECULAR DETERMINANTS; SODIUM-CHANNELS; PEPTIDE TOXINS; SENSITIVITY;

D O I：

10.1016/j.cell.2010.03.052

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：

Toxins have evolved to target regions of membrane ion channels that underlie ligand binding, gating, or ion permeation, and have thus served as invaluable tools for probing channel structure and function. Here, we describe a peptide toxin from the Earth Tiger tarantula that selectively and irreversibly activates the capsaicin- and heat-sensitive channel, TRPV1. This high-avidity interaction derives from a unique tandem repeat structure of the toxin that endows it with an antibody-like bivalency. The "double-knot" toxin traps TRPV1 in the open state by interacting with residues in the presumptive pore-forming region of the channel, highlighting the importance of conformational changes in the outer pore region of TRP channels during activation.

引用

页码：834 / 845

页数：12

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