The Contribution of the Ankyrin Repeat Domain of TRPV1 as a Thermal Module.

Abstract:

:The TRPV1 cation nonselective ion channel plays an essential role in thermosensation and perception of other noxious stimuli. TRPV1 can be activated by low extracellular pH, high temperature, or naturally occurring pungent molecules such as allicin, capsaicin, or resiniferatoxin. Its noxious thermal sensitivity makes it an important participant as a thermal sensor in mammals. However, details of the mechanism of channel activation by increases in temperature remain unclear. Here, we used a combination of approaches to try to understand the role of the ankyrin repeat domain (ARD) in channel behavior. First, a computational modeling approach by coarse-grained molecular dynamics simulation of the whole TRPV1 embedded in a phosphatidylcholine and phosphatidylethanolamine membrane provides insight into the dynamics of this channel domain. Global analysis of the structural ensemble shows that the ARD is a region that sustains high fluctuations during dynamics at different temperatures. We then performed biochemical and thermal stability studies of the purified ARD by the means of circular dichroism and tryptophan fluorescence and demonstrate that this region undergoes structural changes at similar temperatures that lead to TRPV1 activation. Our data suggest that the ARD is a dynamic module and that it may participate in controlling the temperature sensitivity of TRPV1.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Ladrón-de-Guevara E,Dominguez L,Rangel-Yescas GE,Fernández-Velasco DA,Torres-Larios A,Rosenbaum T,Islas LD

doi

10.1016/j.bpj.2019.10.041

subject

Has Abstract

pub_date

2020-02-25 00:00:00

pages

836-845

issue

4

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(19)30905-1

journal_volume

118

pub_type

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