N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F16%3A00461578" target="_blank" >RIV/67985823:_____/16:00461578 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1038/srep28700" target="_blank" >http://dx.doi.org/10.1038/srep28700</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep28700" target="_blank" >10.1038/srep28700</a>

Result language

angličtina

Original language name

N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel

Original language description

Human transient receptor potential ankyrin channel 1 (TRPA1) is a polymodal sensor implicated in pain, inflammation and itching. An important locus for TRPA1 regulation is the cytoplasmic N-terminal domain, through which various exogenous electrophilic compounds such as allyl-isothiocyanate from mustard oil or cinnamaldehyde from cinnamon activate primary afferent nociceptors. This major region is comprised of a tandem set of 17 ankyrin repeats (AR1-AR17), five of them contain a strictly conserved T/SPLH tetrapeptide motif, a hallmark of an important and evolutionarily conserved contribution to conformational stability. Here, we characterize the functional consequences of putatively stabilizing and destabilizing mutations in these important structural units and identify AR2, AR6, and AR11-13 to be distinctly involved in the allosteric activation of TRPA1 by chemical irritants, cytoplasmic calcium, and membrane voltage. Considering the potential involvement of the T/SP motifs as putative phosphorylation sites, we also show that proline-directed Ser/Thr kinase CDK5 modulates the activity of TRPA1, and that T673 outside the AR-domain is its only possible target. Our data suggest that the most strictly conserved N-terminal ARs define the energetics of the TRPA1 channel gate and contribute to chemical-, calcium- and voltage-dependence.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

—

Project

<a href="/en/project/GA15-15839S" target="_blank" >GA15-15839S: Regulatory mechanisms of nociceptive transient receptor potential ion channels</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

6

Issue of the periodical within the volume

Jun 27

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

—

UT code for WoS article

000378490600002

EID of the result in the Scopus database

2-s2.0-84976573602