The characterization of a novel S100A1 binding site in the N-terminus of TRPM1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F16%3A00462408" target="_blank" >RIV/86652036:_____/16:00462408 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/16:00462408 RIV/61388971:_____/16:00462408 RIV/61388963:_____/16:00463996 RIV/00216208:11310/16:10334467

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.biocel.2016.07.014" target="_blank" >http://dx.doi.org/10.1016/j.biocel.2016.07.014</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biocel.2016.07.014" target="_blank" >10.1016/j.biocel.2016.07.014</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The characterization of a novel S100A1 binding site in the N-terminus of TRPM1

Popis výsledku v původním jazyce

Transient receptor potential melastatin-1 channel (TRPM1) is an important mediator of calcium influx into the cell that is expressed in melanoma and ON-bipolar cells. Similar to other members of the TRP channel family, the intracellular N- and C- terminal domains of TRPM1 are expected to play important roles in the modulation of TRPM1 receptor function. Among the most commonly occurring modulators of TRP channels are the cytoplasmically expressed calcium binding proteins calmodulin and S100 calcium-binding protein A1 (S100A1), but the interaction of TRPM1 with S100A1 has not been described yet. Here, using a combination of biophysical and bioinformatics methods, we have determined that the N-terminal L242-E344 region of TRPM1 is a S100A1 binding domain. We show that formation of the TRPM1/S100A1 complex is calcium-dependent. Moreover, our structural model of the complex explained data obtained from fluorescence spectroscopy measurements revealing that the complex formation is facilitated through interactions of clusters positively charged (K271A, R273A, R274A) and hydrophobic (L263A, V270A, L276A) residues at the N-terminus of TRPM1. Taken together, our data suggest a molecular mechanism for the potential regulation of TRPM1 by S100A1.

Název v anglickém jazyce

The characterization of a novel S100A1 binding site in the N-terminus of TRPM1

Popis výsledku anglicky

Transient receptor potential melastatin-1 channel (TRPM1) is an important mediator of calcium influx into the cell that is expressed in melanoma and ON-bipolar cells. Similar to other members of the TRP channel family, the intracellular N- and C- terminal domains of TRPM1 are expected to play important roles in the modulation of TRPM1 receptor function. Among the most commonly occurring modulators of TRP channels are the cytoplasmically expressed calcium binding proteins calmodulin and S100 calcium-binding protein A1 (S100A1), but the interaction of TRPM1 with S100A1 has not been described yet. Here, using a combination of biophysical and bioinformatics methods, we have determined that the N-terminal L242-E344 region of TRPM1 is a S100A1 binding domain. We show that formation of the TRPM1/S100A1 complex is calcium-dependent. Moreover, our structural model of the complex explained data obtained from fluorescence spectroscopy measurements revealing that the complex formation is facilitated through interactions of clusters positively charged (K271A, R273A, R274A) and hydrophobic (L263A, V270A, L276A) residues at the N-terminus of TRPM1. Taken together, our data suggest a molecular mechanism for the potential regulation of TRPM1 by S100A1.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

International Journal of Biochemistry and Cell Biology

ISSN

1357-2725

e-ISSN

—

Svazek periodika

78

Číslo periodika v rámci svazku

Sep 2016

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

186-193

Kód UT WoS článku

000383297300020

EID výsledku v databázi Scopus

2-s2.0-84978764801