Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F00%3A00003720" target="_blank" >RIV/00216208:11120/00:00003720 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1074/jbc.M007848200" target="_blank" >http://dx.doi.org/10.1074/jbc.M007848200</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1074/jbc.M007848200" target="_blank" >10.1074/jbc.M007848200</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors

Popis výsledku v původním jazyce

The gamma -amino-n-butyric acid type B (GABA(B)) receptor is composed of two subunits, GABA(B)1 and GABA(B)2, belonging to the family 3 heptahelix receptors. These proteins possess two domains, a seven transmembrane core and an extracellular domain containing the agonist binding site. This binding domain is likely to fold like bacterial periplasmic binding proteins that are constituted of two lobes that close upon ligand binding. Here, using molecular modeling and site-directed mutagenesis, we have identified residues in the GABA(B)1 subunit that are critical for agonist binding and activation of the heteromeric receptor. Our data suggest that two residues (Ser(246) and Asp(471)) located within lobe I form H bonds and a salt bridge with carboxylic andamino groups of GABA, respectively, demonstrating the pivotal role of lobe I in agonist binding. Interestingly, our data also suggest that a residue within lobe II (Tyr(366)) interacts with the agonists in a closed form model of the bindi

Název v anglickém jazyce

Mapping the agonist-binding site of GABAB type 1 subunit sheds light on the activation process of GABAB receptors

Popis výsledku anglicky

The gamma -amino-n-butyric acid type B (GABA(B)) receptor is composed of two subunits, GABA(B)1 and GABA(B)2, belonging to the family 3 heptahelix receptors. These proteins possess two domains, a seven transmembrane core and an extracellular domain containing the agonist binding site. This binding domain is likely to fold like bacterial periplasmic binding proteins that are constituted of two lobes that close upon ligand binding. Here, using molecular modeling and site-directed mutagenesis, we have identified residues in the GABA(B)1 subunit that are critical for agonist binding and activation of the heteromeric receptor. Our data suggest that two residues (Ser(246) and Asp(471)) located within lobe I form H bonds and a salt bridge with carboxylic andamino groups of GABA, respectively, demonstrating the pivotal role of lobe I in agonist binding. Interestingly, our data also suggest that a residue within lobe II (Tyr(366)) interacts with the agonists in a closed form model of the bindi

Druh

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

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2000

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

—

Svazek periodika

275

Číslo periodika v rámci svazku

52

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

41166-41174

Kód UT WoS článku

000166114600069

EID výsledku v databázi Scopus

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