IDPfun — Driving the functional characterization of intrinsically disordered proteins

Results in brief

Driving the functional characterization of intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) are proteins that lack a fixed three-dimensional shape or conformation and can instead adapt in response to interactions with other molecules or changes in the environment. Unlike well-structured globular proteins, which engage in stable interactions, IDPs primarily engage in transient interactions. This unique property allows IDPs to perform a diverse range of molecular functions. Their ability to undergo shape adaptation enables promiscuous interactions with multiple targets, making them crucial for orchestrating cellular processes. Consequently, IDPs often serve as central nodes in the protein-protein interaction network within cells and are attractive targets for manipulating cellular regulation. IDPs are widespread in eukaryotes, being encoded by about one-third of the total genetic material. They play a significant role in various diseases and offer untapped potential for drug development. Despite their importance, IDPs remain poorly characterized due to significant challenges encountered in both experimental and computational studies. Capturing the properties of dynamic systems is challenging at the experimental level, while modeling IDPs is difficult computationally due to the lack of standardized and integrated data. Computational methods have aided in identifying IDPs based on their amino acid sequences, and curated databases dedicated to IDPs have provided a starting point for their analysis. However, our functional understanding of IDPs remains limited. Advancing our knowledge of IDPs has substantial societal impact, given their involvement in numerous diseases.IDPfun is an international consortium focused on expanding our understanding of IDP functions. The consortium was established based on fruitful collaborations initiated during the NGP-net COST Action (2015-2019). Leveraging existing state-of-the-art computational tools and databases, many of which were developed by IDPfun members, the consortium provided a collaborative environment for researching novel approaches to model different aspects of IDP behavior and enhance the accessibility of IDP data.

Data: CORDIS, © European Union

Project objective

Intrinsically disordered proteins (IDPs), characterized by high conformational variability and interaction promiscuity, defy the classic protein structure-function paradigm. IDPs cover almost half of the residues in Eukaryotic proteomes. Growing evidence suggests that IDPs, interacting with multiple partners, are major players in cellular regulation and involved in numerous human diseases. Computational methods have contributed to the identification of IDPs from sequence and recently published curated IDP databases provide a starting point. However, functional knowledge for IDPs remains very limited.IDPfun is an international consortium aiming to extend our knowledge on the functions of IDPs. Starting from available state of the art computational tools and databases, which have been mostly developed by IDPfun participants, it aims drive a new level of IDP characterization leverage the complementary expertise of 5 EU MS and 3 TC institutions in Argentina, the latter providing useful complementary expertises. IDPfun will create a collaborative environment for research on novel ways to detect and characterize different IDP phenomena in their evolutionary context. It will develop an ontology and classification facilitating the comprehension of IDP complexity and aims to understand IDP functional mechanisms. The gained knowledge will be translated into major international protein databases for the benefit of the wider scientific community. Periodic meetings and symposia will generate a continuous knowledge exchange to be disseminated by open training schools and conferences. IDPfun will foster particularly young researchers, through dedicated activities and by ensuring adherence to the highest quality, ethics and gender balance standards. It is expected that IDPfun will strengthen overseas collaborations, focusing and coordinating research, leading to the creation of a sustainable international IDP community, driving knowledge and infrastructure in bioinformatics.

Original text from CORDIS.

Participants

UNIVERSITA DEGLI STUDI DI PADOVA · PadovaCoordinatorItaly
EOTVOS LORAND TUDOMANYEGYETEM · BudapestHungary
EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergGermany
FUNDACION INSTITUTO LELOIR · Buenos AiresArgentina
UNIVERSIDAD NACIONAL DE GENERAL SAN MARTIN · San Martin Buenos AiresArgentina
UNIVERSIDAD NACIONAL DE QUILMES · BernalArgentina
UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN · DublinIreland
VRIJE UNIVERSITEIT BRUSSEL · Bruxelles / BrusselBelgium

IDPfun · Driving the functional characterization of intrinsically disordered proteins

Results in brief

Driving the functional characterization of intrinsically disordered proteins

Project objective

Participants

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