Objetivo Ion channels are proteins composed of a hydrophillic pore that facilitate ion flow across a plasma membrane. This ionic permeability is controlled by a set of essential properties affecting the channel activation and inactivation in response to voltage, ligands, or intracellular second messengers. The focus of the present project proposal, the transient receptor potential vanilloid channel (TRPV5), forms a specific category within the large TRP familiy of ion channels as it comprises a unique high selectivity for calcium ions together with a calcium-dependent inactivation mechanism that is incompletely understood. Detailed analysis of the TRPV5 channel will provide new structural insights into channel gating that can be extrapolated to other TRP channels, as the current knowledge on the TRP protein structure and its impact on the regulation of the channel function is still limited. The key objective of my project is to deliver the first detailed mechanistic view of TRPV5 by connecting Prof. Cheng’s expertise in structural biology with my biophysical background on TRP channel functioning. The following work packages will be addressed:1) Channel activation mechanism of TRPV5Elucidation of the 3D structure of integral TRPV5 by single-particle cryo-EM will provide critical structural and mechanistic insight into calcium-dependent regulation of channel function.2) Intramolecular regulation of TRPV5Reconstitution of TRPV5 into lipid nanodiscs and liposomes allows detailed study on lipid regulation and the mechanism of channel inactivationTaken together, this project focuses on the structure-function analysis of TRPV5, a distinctive calcium-selective TRP channel. The goal is to elucidate the structure of the TRPV5 channel, and to unravel functional domains that are involved in channel function at the mechanistic level. This will ultimately advance our understanding of the molecular differences of activation, ion permeation and gating of TRP channels. Ámbito científico natural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesmolecular biologystructural biology Programa(s) 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 Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-GF - Global Fellowships Coordinador STICHTING RADBOUD UNIVERSITEIT Aportación neta de la UEn € 162 864,60 Dirección HOUTLAAN 4 6525 XZ Nijmegen Países Bajos Ver en el mapa Región Oost-Nederland Gelderland Arnhem/Nijmegen Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 162 864,60 Socios (1) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo Socio Las organizaciones asociadas contribuyen a la aplicación de la acción, pero no firman el acuerdo de subvención. THE REGENTS OF THE UNIVERSITY OF CALIFORNIA Estados Unidos Aportación neta de la UEn € 0,00 Dirección FRANKLIN STREET 1111 12 FLOOR 94607 OAKLAND CA Ver en el mapa Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 80 065,20
