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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.

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

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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