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chemREPEAT SIGNED

Structure and Dynamics of Low-Complexity Regions in Proteins: The Huntingtin Case

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EC-Contrib. €

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 chemREPEAT project word cloud

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

intervention    lcr    pathologies    acid    localized    incorporate    chemrepeat    stretches    capacity    perform    positions    biology    deadly    hosting    integrating    repetitions    tract    residues    homorepeats    few    played    strategies    dimensional    probes    derive    data    expand    unveil    first    pave    acids    biophysical    time    conformational    relationships    proteins    unnatural    severe    reveal    functions    consecutive    hosts    labelled    lcrs    35    relevance    facilitated    disease    rational    eukaryotes    linked    designed    function    limitations    glutamine    enrichment    computational    property    appearing    prototype    glutamines    hd    regions    ensembles    huntingtin    repetitive    constructions    roles    intrinsic    frontiers    hampered    abnormally    htt    protein    specialized    flanking    despite    huntington    dynamics    contrast    atomic    degeneracy    complementary    characterization    structural    amino    flexibility    isotopically    physicochemical    experimental    diseases    neuropathology    subfamily    play    tools    threshold    pathological    resolution    structure    complexity    bases    techniques    environments    individuals    synergistically    overcome    enriched   

Project "chemREPEAT" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

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 France [FR]
 Total cost 1˙999˙844 €
 EC max contribution 1˙999˙844 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙999˙844.00

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 Project objective

Proteins hosting regions highly enriched in one or few amino acids, the so-called Low-Complexity Regions (LCR), are very common in eukaryotes and play crucial roles in biology. Homorepeats, a subfamily of LCR that present stretches of the same amino acid, perform very specialized functions facilitated by the localized enrichment of the same physicochemical property. In contrast, numerous severe pathologies have been associated to abnormally long repetitions. Despite the relevance of homorepeats, their high-resolution characterization by traditional structural biology techniques is hampered by the degeneracy of the amino acid environments and their intrinsic flexibility. In chemREPEAT, I will develop strategies to incorporate isotopically labelled and unnatural amino acids at specific positions within homorepeats that will overcome present limitations. These labelled positions will be unique probes to investigate for first time the structure and dynamics of homorepeats at atomic level using complementary biophysical techniques. Computational tools will be specifically developed to derive three-dimensional conformational ensembles of homorepeats by synergistically integrating experimental data. chemREPEAT strategies will be developed on huntingtin (Htt), the prototype of repetitive protein. Htt hosts a glutamine tract that is linked with Huntington’s disease (HD), a deadly neuropathology appearing in individuals with more than 35 consecutive Glutamine residues that represent a pathological threshold. The application of the developed approaches to several Htt constructions with different number of Glutamines will reveal the structural bases of the pathological threshold in HD and the role played by the regions flanking the Glutamine tract. The strategies designed in chemREPEAT will expand present frontiers of structural biology to unveil the structure/function relationships for LCRs. This capacity will pave the way for a rational intervention in associated diseases.

 Publications

year authors and title journal last update
List of publications.
2017 Tiago N Cordeiro, Fátima Herranz-Trillo, Annika Urbanek, Alejandro Estaña, Juan Cortés, Nathalie Sibille, Pau Bernadó
Small-angle scattering studies of intrinsically disordered proteins and their complexes
published pages: 15-23, ISSN: 0959-440X, DOI: 10.1016/j.sbi.2016.10.011
Current Opinion in Structural Biology 42 2020-03-20
2018 Annika Urbanek, Anna Morató, Frédéric Allemand, Elise Delaforge, Aurélie Fournet, Matija Popovic, Stephane Delbecq, Nathalie Sibille, Pau Bernadó
A General Strategy to Access Structural Information at Atomic Resolution in Polyglutamine Homorepeats
published pages: 3598-3601, ISSN: 1433-7851, DOI: 10.1002/anie.201711530
Angewandte Chemie International Edition 57/14 2020-03-20
2018 Alejandro Estaña, Kevin Molloy, Marc Vaisset, Nathalie Sibille, Thierry Siméon, Pau Bernadó, Juan Cortés
Hybrid parallelization of a multi-tree path search algorithm: Application to highly-flexible biomolecules
published pages: 84-100, ISSN: 0167-8191, DOI: 10.1016/j.parco.2018.06.005
Parallel Computing 77 2020-03-20

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