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Atomic Resolution Structures of Mitochondrial Respiratory Chain Supercomplexes

Total Cost €


EC-Contrib. €






 RSC project word cloud

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

biochemical    nadh    fei    laboratory    oxygen    detector    systematic    rcss    microscope    chain    techniques    spectrometric    mackinnon    membrane    spectroscopy    vienna    iii2    assemblies    resolution    mv    macromolecular    biocenter    preliminary    austria    mammalian    mitochondria    particle    mitochondrial    disruptive    crystallography    map    collaborators    opportunity    ist    15    form    em    detergents    molecular    aring    protein    inner    gatan    collected    respiratory    structures    rscs    positioned    responsible    data    aries    iv2    determined    cryo    blotting    lmb    purified    controversial    me    10    dr    polara    compare    roderick    supercomplexes    microscopy    preparation    single    ray    direct    varying    biology    ovis    physiological    characterisation    electron    physiology    atomic    k2    grid    samples    nmr    mass    particles    associate    structure    push    shown    mainly    poorly    density    complexes    leonid    presently    300    rcs    sazanov    transport   

Project "RSC" data sheet

The following table provides information about the project.


Organization address
address: Am Campus 1
postcode: 3400

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 Austria [AT]
 Project website
 Total cost 178˙156 €
 EC max contribution 178˙156 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2018-08-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

The objectives of this proposal are to determine atomic-resolution structures of mammalian mitochondrial respiratory chain supercomplexes (RCSs) by single particle electron cryo-microscopy (cryo-EM). It has been shown that the large protein complexes of the inner mitochondrial membrane responsible for electron transport from NADH to molecular oxygen (complexes I, III and IV) associate to form three major RCSs: I/III2, III2/IV2 and I/III2/IV. Currently, the physiological role of the RSCs is controversial and poorly understood. Atomic-resolution structures of the RSCs will be essential for fully understanding their physiology. Presently I have generated a 15 Å cryo-EM density map for RCS I/III2/IV from ~10,000 particles purified from Ovis aries mitochondria. Our preliminary data show that in order to push the resolution we will need to improve both the biochemical preparation of the RCS particles as well as the cryo-EM grid preparation. This will be done through systematic biochemical characterisation of the RCSs in different non-disruptive detergents and systematic grid preparation varying grid type and blotting conditions. In addition to RCS I/III2/IV, the structure of RCS I/III2 will be determined. High-resolution cryo-EM data will be collected at the Vienna Biocenter using the FEI Polara 300 mV microscope with Gatan K2 direct electron detector. In order to fully compare the make-up of the different RCSs mass spectrometric analysis will be carried out on the purified samples by our collaborators at the Laboratory for Molecular Biology (LMB). My previous experience in the laboratory of Dr Roderick MacKinnon mainly focused on membrane protein structure determination by X-ray crystallography and NMR spectroscopy. The opportunity to work at the IST Austria with Dr Leonid Sazanov will allow me to learn state of the art cryo-EM techniques, which are positioned to be the future of atomic-resolution structure determination for large macromolecular assemblies.


year authors and title journal last update
List of publications.
2016 James A. Letts, Karol Fiedorczuk, Leonid A. Sazanov
The architecture of respiratory supercomplexes
published pages: 644-648, ISSN: 0028-0836, DOI: 10.1038/nature19774
Nature 537/7622 2019-06-13
2016 Fiedorczuk, Karol; Degliesposti, Gianluca; Sazanov, Leonid A.; Skehel, Mark; Letts, James A
Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation
published pages: , ISSN: 1083-351X, DOI: 10.1074/jbc.M116.735142
Journal of Biological Chemistry 1 2019-06-13

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