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BENDER SIGNED

BiogENesis and Degradation of Endoplasmic Reticulum proteins

Total Cost €

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EC-Contrib. €

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Partnership

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 BENDER project word cloud

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

depletion    provides    complexity    biology    sub    conformations    cryo    diseases    tomograms    bio    favours    stress    disorders    proteasome    computational    oligomerization    macromolecule    blueprint    reticulum    evasion    free    stabilization    aging    im    electron    cet    maximum    nascent    26s    tomography    classification    microenvironment    network    endoplasmic    leverage    degradation    homeostasis    structure    immune    biogene    chaperone    regulation    transferase    genesis    subnanometer    gateway    molecular    misfolded    silico    cells    mrna    complexes    bound    mediated    resolution    folding    3d    residing    facilitates    histocompatibility    structural    surrounding    macromolecules    class    mhc    viral    ing    protein    sophisticated    model    import    oligosaccharyl    dynamic    membrane    subtomogram    sis    substrate    maturation    glycosylation    mechanistic    intricate    purification    insights    diabetes    depicting    cotranslational    eukaryotic    ire1    cellular    pioneered    native    cell    chronic    neurodegenerative    translation    proteins    machinery    cytosolic    reveal    translocon    details    er    cytomegalovirus   

Project "BENDER" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT UTRECHT 

Organization address
address: HEIDELBERGLAAN 8
city: UTRECHT
postcode: 3584 CS
website: www.uu.nl

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 Netherlands [NL]
 Total cost 2˙496˙611 €
 EC max contribution 2˙496˙611 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT UTRECHT NL (UTRECHT) coordinator 2˙496˙611.00

Map

 Project objective

The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes. I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d. This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.

 Publications

year authors and title journal last update
List of publications.
2018 Katharina Braunger, Stefan Pfeffer, Shiteshu Shrimal, Reid Gilmore, Otto Berninghausen, Elisabet C. Mandon, Thomas Becker, Friedrich Förster, Roland Beckmann
Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum
published pages: 215-219, ISSN: 0036-8075, DOI: 10.1126/science.aar7899
Science 360/6385 2019-06-11
2018 Patrique Praest, A. Manuel Liaci, Friedrich Förster, Emmanuel J.H.J. Wiertz
New insights into the structure of the MHC class I peptide-loading complex and mechanisms of TAP inhibition by viral immune evasion proteins
published pages: , ISSN: 0161-5890, DOI: 10.1016/j.molimm.2018.03.020
Molecular Immunology 2019-06-11

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