Integrating disorder in globular multidomain proteins: Fuzzy sensors and the role of SH3 domains

Intrinsically disordered proteins represent about one third of eukaryotic proteins. An additional third correspond to proteins containing folded domains as well as large intrinsically disordered regions (IDR). While IDRs may represent functionally autonomous domains, in some instances it has become...

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Bibliographic Details
Authors: Arbesú Andrés, Miguel, Pons Vallès, Miquel
Format: article
Status:Versión aceptada para publicación
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/149462
Online Access:https://hdl.handle.net/2445/149462
Access Level:Open access
Keyword:Proteïnes quinases
Cèl·lules eucariotes
Protein kinases
Eukaryotic cells
Description
Summary:Intrinsically disordered proteins represent about one third of eukaryotic proteins. An additional third correspond to proteins containing folded domains as well as large intrinsically disordered regions (IDR). While IDRs may represent functionally autonomous domains, in some instances it has become clear that they provide a new layer of regulation for the activity displayed by the folded domains. The sensitivity of the conformational ensembles defining the properties of IDR to small changes in the cellular environment and the capacity to modulate this response through post-translational modifications makes IDR ideal sensors enabling continuous, integrative responses to complex cellular inputs. Folded domains (FD), on the other hand, are ideal effectors, e.g. by catalyzing enzymatic reactions or participating in binary on/off switches. In this perspective review we discuss the possible role of intramolecular fuzzy complexes to integrate the very different dynamic scales of IDR and FD, inspired on the recent observations of such dynamic complexes in Src family kinases, and we explore the possible general role of the SH3 domains connecting IDRs and FD.