HSP90NMR

"The study of Hsp90 through the use of nuclear magnetic resonance, small angle scattering and calorimetry."

Coordinatore	HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH    more  Organization address address: Ingolstaedter Landstrasse 1 city: MUENCHEN postcode: 85764 contact info Titolo: Dr. Nome: Jürgen Cognome: Ertel Email: send email Telefono: +49 89 3187 3022
Nazionalità Coordinatore	Germany [DE]
Totale costo	167˙390 €
EC contributo	167˙390 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-IIF
Funding Scheme	MC-IIF
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-02-01   -   2015-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH  Organization address address: Ingolstaedter Landstrasse 1 city: MUENCHEN postcode: 85764 contact info Titolo: Dr. Nome: Jürgen Cognome: Ertel Email: send email Telefono: +49 89 3187 3022	DE (MUENCHEN)	coordinator	167˙390.40

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 Obiettivo del progetto (Objective)

'Proper protein folding is essential for cellular homeostasis. Cells employ a large array of chaperones to ensure protein adopt the proper conformation. Hsp90 is an important chaperone and comprises of 1-2% of all protein is eukaryotic cells. Additionally, Hsp90 is upregulated in cancerous cells to facilitate fast proliferation. There are several X-ray crystal structures available for Hsp90 free in solution and interacting with its target proteins. This combined with small angle x-ray/neutron scattering (SAXS/SANS) and Förster resonance energy transfer (FRET) data, demonstrate that HSP90 is a 90 kDa dimeric protein and undergoes large conformational changes throughout its function. However, these crystal structures only provide a static picture of Hsp90 function so the molecular and dynamic details of these rearrangements are not well understood. We will employ nuclear magnetic resonance spectroscopy (NMR) as a method to further probe these changes. NMR can provide atomically resolved real time information of Hsp90 in solution either free or interacting with its targets. Hsp90 contains three distinct domains, and we have individually isotopically label each domain. This will allow each domain to be studied either independently or and in tandem with neighbouring domains. Also a target protein, the glucocorticoid receptor (GR) protein, will be introduced to observe how the behaviour of each domain changes upon binding a client protein. Through observing the changes in chemical shifts and relaxation rates we will be able to identify specific regions in Hsp90 which are involved in the binding of client proteins. We will also employ SAXS/SANS experiments to observe changes in orientation of the domains when interacting with the GR protein, and use isothermal titration calorimetry to determine the thermodynamic parameters of Hsp90 binding the GR protein. Through combining all of these techniques we hope to gain a broader understanding of Hsp90 function.'