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MHCIbiopic SIGNED

MHC-I biogenesis and degradation at the endoplasmic reticulum membrane

Total Cost €

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EC-Contrib. €

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Partnership

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 MHCIbiopic project word cloud

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

xl    loaded    translationally    community    free    electron    recognition    trimeric    extend    assembles    stabilized    assays    endoplasmic    microbial    start    heavy    opportunity    basic    contributions    vitro    ray    length    cet    blooming    eukaryotic    cryo    spectrometry    viral    ultimately    crystallography    secretory    exported    proteostasis    independent    largely    situ    hcmv    assisted    lack    surface    functional    molecular    calnexin    us2    membrane    ms    substrate    integrative    immune    tumors    linking    biogenesis    combine    larger    chaperones    scientific    data    insertion    complexes    degradation    network    possibly    erad    maturation    folding    us11    formed    researcher    unravel    structural    proteome    er    critical    utilizes    erp57    reticulum    cell    leader    stress    viruses    histocompatibility    cd8    nascent    membranes    once    mhc    chain    mass    one    co    cellular    hetero    cells    cytomegalovirus    tomography    cross    transiently    light    tapasin    peptide    microsomal    diseases    scales    assembly    association    model    entrance    proteins    trigger    assemblies    career    translocation    mechanism    picture    oligomeric    protein    human    immunoevasins   

Project "MHCIbiopic" 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 165˙598 €
 EC max contribution 165˙598 € (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 2019-02-01   to  2021-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT UTRECHT NL (UTRECHT) coordinator 165˙598.00

Map

 Project objective

One third of the cell proteome utilizes the secretory pathway for entrance into the endoplasmic reticulum (ER). However, the insertion of nascent proteins into or their translocation across the ER membrane, their maturation and assembly to oligomeric complexes and their degradation are very basic cellular processes of which we largely lack an integrative structural insight. I propose to use Cryo Electron Tomography (CET) to unravel the molecular mechanism of the biogenesis and degradation of Major Histocompatibility Complex-I (MHC-I) as a model substrate in situ. MHC-I are critical for immune responses to viruses and tumors. They are hetero-trimeric complexes formed by a light chain, a heavy chain and a variable cellular or microbial peptide. MHC-I folding is assisted by the chaperones ERp57 and calnexin at the ER membrane, where it assembles co-translationally, stabilized by tapasin. Once loaded with a peptide, MHC-I is exported to the cell surface for recognition by CD8 T-cells. However, some viral immunoevasins like the human cytomegalovirus (HCMV) proteins US2 and US11 trigger the ER-Associated Degradation (ERAD) of MHC-I. I will combine data from CET, cross linking mass spectrometry (XL-MS) and in vitro functional assays on eukaryotic cellular and microsomal cell-free systems to provide an integrated picture of the complexes transiently involved in these processes. This work will make great contributions to our molecular understanding of cellular proteostasis and possibly provide novel molecular targets addressing diseases associated with ER stress. The proposed project will extend my knowledge from protein X-ray crystallography to the study of more complex molecular assemblies in association with membranes at larger length scales – ultimately the cell. Taken together, this project represents a unique opportunity to start blooming in my career as an independent researcher with a strong european network, and become a leader in the scientific community.

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

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