Opendata, web and dolomites


BiogENesis and Degradation of Endoplasmic Reticulum proteins

Total Cost €


EC-Contrib. €






 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.

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

Project "BENDER" data sheet

The following table provides information about the project.


Organization address
postcode: 3584 CS

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


Take a look of project's partnership.

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


 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.


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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