Structural Dynamics of Membrane Receptors at native-like conditions

Información del proyecto

DYNAMO

Identificador del acuerdo de subvención: 753487

DOI

10.3030/753487

Proyecto finalizado el 10 Febrero 2018

Fecha de la firma de la CE 23 Marzo 2017

Fecha de inicio 1 Marzo 2018

Fecha de finalización 29 Febrero 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 212 194,80

Aportación de la UE

€ 212 194,80

Coordinado por

KOBENHAVNS UNIVERSITET
Denmark

Objetivo

Proteins embedded in cell membranes are vital signaling and trafficking platforms connecting the outside to the inside of a cell, and functioning as primary drug targets. DYNAMO is an integrative dynamic structural biology project, with the ambitious goal of developing and implementing comprehensive experimental and computational approaches for studying the structural dynamics of membrane receptors (MRs) and their complexes at native-like conditions. DYNAMO is highly interdisciplinary, combining protein chemistry and computational physics to study dynamical processes underlying the function of MRs, and is designed to combine the expertise of the fellow and host. The project will establish an integrated platform based on the nanodisc-technology and the combined use of low- and high-resolution structural biology techniques to bring unique and alternative insights into the structural dynamics of MRs containing ”fuzzy” (i.e highly flexible) domains, and the role this plays in functional signaling assemblies. In order to broaden the scope of the project and secure a general applicability of the developed methodology, full-length tissue Factor (TF) and Ghrelin receptor (GHS-R1a) are selected as models of single-pass and multi-pass MRs. These MRs do not only display different topologies and functional assemblies but also different selectivity towards lipids. TF and GHS-R1a are central to blood coagulation and energy homeostasis, respectively, and also connected to genetic and metabolic disorders, and thereby not only relevant as model systems but also promising drug targets. The project will exploit the recent advances in SAXS/SANS- and NMR-based methods to study the TF and GHS-R1a in nanodiscs, with an emphasis on their conformational ensemble nature. Upon the establishment of the methodology, it will be extended to study the interaction with their endogenous ligands.

Ámbito científico (EuroSciVoc)

• ciencias naturales › matemáticas › matemáticas puras › topología
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › lípidos
• ciencias médicas y de la salud › medicina básica › fisiología › homeostasis
• ciencias naturales › ciencias biológicas › biología molecular › biología estructural

Palabras clave

• Tissue factor
• GPCRs
• Conformational dynamics
• Membrane-mimics
• Nanodisc-Technology
• Integrative Structural Biology
• Biomolecular NMR
• Neutron and X-ray scattering

Programa(s)

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

Tema(s)

• MSCA-IF-2016 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2016

Coordinador

KOBENHAVNS UNIVERSITET

• Aportación neta de la UEn: € 212 194,80
• Dirección: NORREGADE 10 ; 1165 KOBENHAVN ; Dinamarca
• Región: Danmark › Hovedstaden › Byen København
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 212 194,80