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RespViRALI SIGNED

Structural and functional insights into the assembly of respiratory complexes by a novel putative chaperone

Total Cost €

EC-Contrib. €

Partnership

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RespViRALI project word cloud

Explore the words cloud of the RespViRALI project. It provides you a very rough idea of what is the project "RespViRALI" about.

complexes central latest protein solved elucidate ray despite enigmatic diseases atomic reported respiratory front universal scientific humans enterobacterial play components interactions source affinity es electron biophysical mechanisms negative assembly angle capital huge strategies stain particle physical structures subunits biology individual employ small formed single antibiotics structural reminiscent resistance cryo infection bacterial examine cage resolution linked neurodegenerative literature energy cryoem life cellular host crystallography insights dissect bacteria machine groel molecular chaperone scattering macromolecular defects folding functional showed kinetics neutron architecture assisted microscopy implication stress atp situated line unexplored coli team form

Project "RespViRALI" data sheet

The following table provides information about the project.

Coordinator	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Organization address address: RUE MICHEL ANGE 3 city: PARIS postcode: 75794 website: www.cnrs.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	France [FR]
Total cost	173˙076 €
EC max contribution	173˙076 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2017
Funding Scheme	MSCA-IF-EF-ST
Starting year	2019
Duration (year-month-day)	from 2019-07-01 to 2021-06-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Organization address address: RUE MICHEL ANGE 3 city: PARIS postcode: 75794 website: www.cnrs.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	173˙076.00

Map

Project objective

Cellular respiratory complexes play a central role in the production of ATP, the universal energy source of life. Defects in their activity are linked to neurodegenerative diseases in humans and antibiotics resistance in bacteria. Despite their capital importance, the assembly mechanisms of respiratory complexes remain highly unexplored.

This research project aims to investigate how the assembly of the major bacterial respiratory Complex I is assisted by a multi protein system involved in enterobacterial stress response. The host team recently solved the structures of two components of this system with cryo-electron microscopy (cryoEM) and X-ray crystallography, and showed that they form a huge cage-like assembly reminiscent of the GroEL-ES chaperone. Importantly, the latest scientific literature reported physical interactions between this macromolecular assembly and specific subunits of E. coli respiratory complexes.

To elucidate the functional role of this enigmatic machine in the assembly of Complex I, I will employ a highly integrated approach situated at the front line of molecular structural biology. A wide range of biophysical methods will be used to dissect the affinity and kinetics of individual interactions between components of this multi protein system and subunits of Complex I. I will examine the overall architecture of the formed complexes with negative stain electron microscopy and small-angle X-Ray/Neutron scattering, while atomic resolution insights of the complexes will be provided by high resolution single particle cryoEM and X-ray crystallography.

The structures and functional insights obtained in the proposed project will improve our general understanding of coordination between protein folding and assembly of respiratory complexes, and bring novel insights into their implication in antibiotics resistance and pathways of bacterial stress responses, which are crucial to developing strategies for controlling infection.

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The information about "RESPVIRALI" are provided by the European Opendata Portal: CORDIS opendata.