Allosteric modulation of G-protein Coupled Receptors conformational landscape

Projektinformationen

AlloGPCR

ID Finanzhilfevereinbarung: 799376

DOI 10.3030/799376

Abgeschlossenes Projekt

EK-Unterschriftsdatum 3 Mai 2018

Startdatum 1 September 2018

Enddatum 31 August 2021

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 246 668,40

EU-Beitrag € 246 668,40

Koordiniert durch

UNIVERSITE DE MONTPELLIER
France

Ziel

G protein-coupled receptors (GPCRs) are the largest family of transmembrane receptors in eukaryotes. They bind a wide range of ligands, such as neurotransmitters, hormones, lipids and many others. GPCRs are the target of more than 30% of the drugs currently on the market, addressing neuropsychiatric, cardiovascular, pulmonary and metabolic disorders, cancer, obesity and AIDS.
The functional versatility of GPCRs cannot be explained by a simple two-state model of activation considering only an active and an inactive state, as these receptors are highly dynamic and can explore a wide range of conformations.
Some receptors of the family can signal in the absence of ligand (basal activity), and despite GPCR have been largely studied in the past years, little is known about their signal transduction mechanism.
Apart from ligands and signalling partners, the structure and function of GPCRs can be modulated by lipids.
In this context, our research will be divided in two steps: delineating the role of lipids on GPCR conformational landscape at the molecular scale (Aim1) and exploring an additional allosteric factor in line with lipid composition, the homo- and hetero-receptor oligomerisation (Aim2).
To that purpose, we will apply an integrated, multidisciplinary analysis, to characterize protein dynamics under physiological conditions, with the GPCR reconstituted in model lipid systems or living cells, and in the presence of ligands, signalling and regulatory partners. We will use conformational probes to investigate the effect of lipids and other GPCRs on receptor dynamics, and correlate these findings with functional properties such as agonist binding and G protein coupling.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• natural sciences › biological sciences › biochemistry › biomolecules › lipids
• medical and health sciences › health sciences › infectious diseases › RNA viruses › HIV
• medical and health sciences › clinical medicine › oncology
• medical and health sciences › health sciences › nutrition › obesity

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2017 - Individual Fellowships

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2017

Finanzierungsplan

MSCA-IF-GF - Global Fellowships

Koordinator

UNIVERSITE DE MONTPELLIER

• Netto-EU-Beitrag: € 246 668,40
• Adresse: 163 RUE AUGUSTE BROUSSONNET ; 34090 Montpellier ; Frankreich
• Region: Occitanie › Languedoc-Roussillon › Hérault
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 246 668,40

Partner (1)

Partner

Partnerorganisationen tragen zur Umsetzung der Aktion bei, unterzeichnen jedoch nicht die Finanzhilfevereinbarung.

BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

Vereinigte Staaten

• Netto-EU-Beitrag: € 0,00
• Adresse: SERRA MALL 450 ; 94305 2004 Stanford
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 160 130,40