A combination of computational and experimental approaches reveals the dynamics of ASIC1 gating, involving a deformation of the channel that triggers “twist-to-open” motions of the channel pore

A Taly

AO Samson

B Brooks

BR Brooks

CM Canessa

D Zhang

DA Case

F Tama

Fang Yu

GV Miloshevsky

H Valadie

Huaiyu Yang

Hualiang Jiang

Hui Cao

I Bahar

IH Shrivastava

J Gao

J Jasti

JA Wemmie

K Suhre

M Brandl

MA Friese

MM Tirion

MW Coryell

O Beckstein

O Krishtal

PM Snyder

R Waldmann

Richard W. Aldrich

S Kellenberger

S Sheng

SA Shaikh

T Gaillard

T Li

Tian-Le Xu

Wei-Guang Li

X Cheng

X Liu

Y Shen

Ye Yu

YF Li

ZG Xiong

PLoS Biology

English

PubMed

Yang Huaiyu

Yu Ye

Li Wei-Guang

Yu Fang

Cao Hui

Xu Tian-Le

Jiang Hualiang

Public Library of Science (PLOS)

Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism

The acid-sensing ion channel 1 (ASIC1) is a key receptor for extracellular protons. Although numerous structural and functional studies have been performed on this channel, the structural dynamics underlying the gating mechanism remains unknown. We used normal mode analysis, mutagenesis, and electrophysiological methods to explore the relationship between the inherent dynamics of ASIC1 and its gating mechanism. Here we show that a series of collective motions among the domains and subdomains of ASIC1 correlate with its acid-sensing function. The normal mode analysis result reveals that the intrinsic rotation of the extracellular domain and the collective motions between the thumb and finger induced by proton binding drive the receptor to experience a deformation from the extracellular domain to the transmembrane domain, triggering the channel pore to undergo "twist-to-open" motions. The movements in the transmembrane domain indicate that the likely position of the channel gate is around Leu440. These motion modes are compatible with a wide body of our complementary mutations and electrophysiological data. This study provides the dynamic fundamentals of ASIC1 gating

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Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism.

The acid-sensing ion channel 1 (ASIC1) is a key receptor for extracellular protons. Although numerous structural and functional studies have been performed on this channel, the structural dynamics underlying the gating mechanism remains unknown. We used normal mode analysis, mutagenesis, and electrophysiological methods to explore the relationship between the inherent dynamics of ASIC1 and its gating mechanism. Here we show that a series of collective motions among the domains and subdomains of ASIC1 correlate with its acid-sensing function. The normal mode analysis result reveals that the intrinsic rotation of the extracellular domain and the collective motions between the thumb and finger induced by proton binding drive the receptor to experience a deformation from the extracellular domain to the transmembrane domain, triggering the channel pore to undergo ‘‘twist-to-open’ ’ motions. The movements in the transmembrane domain indicate that the likely position of the channel gate is around Leu440. These motion modes are compatible with a wide body of our complementary mutations and electrophysiological data. This study provides the dynamic fundamentals of ASIC1 gating

Wei-guang Li

Tian-le Xu

CiteSeerX

Crossref

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http://www.dddc.ac.cn/news/journal.pbio.1000151.pdf

Inherent Dynamics of the Acid-Sensing Ion Channel 1 Correlates with the Gating Mechanism

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