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chemREPEAT SIGNED

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

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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.

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

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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