Characterization of Soft Amyloid Cores in Human Prion-Like Proteins
Batlle Carreras, Cristina (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Sánchez de Groot, Natalia (Centre de Regulació Genòmica)
Iglesias, Valentin (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Navarro, Susanna (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2017
Resum:	Prion-like behaviour is attracting much attention due to the growing evidences that amyloid-like self-assembly may reach beyond neurodegeneration and be a conserved functional mechanism. The best characterized functional prions correspond to a subset of yeast proteins involved in translation or transcription. Their conformational promiscuity is encoded in Prion Forming Domains (PFDs), usually long and intrinsically disordered protein segments of low complexity. The compositional bias of these regions seems to be important for the transition between soluble and amyloid-like states. We have proposed that the presence of cryptic soft amyloid cores embedded in yeast PFDs can also be important for their assembly and demonstrated their existence and self-propagating abilities. Here, we used an orthogonal approach in the search of human domains that share yeast PFDs compositional bias and exhibit a predicted nucleating core, identifying 535 prion-like candidates. We selected seven proteins involved in transcriptional or translational regulation and associated to disease to characterize the properties of their amyloid cores. All of them self-assemble spontaneously into amyloid-like structures able to propagate their polymeric state. This provides support for the presence of short sequences able to trigger conformational conversion in prion-like human proteins, potentially regulating their functionality.
Ajuts:	Ministerio de Economía y Competitividad BIO2016-783-78310-R
Nota:	Altres ajuts: ICREA-Academia 2015 to S.V.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Amino Acid Sequence ; Amyloid ; Databases, Protein ; DEAD-box RNA Helicases ; Fungal Proteins ; Humans ; Intracellular Signaling Peptides and Proteins ; Intrinsically Disordered Proteins ; Mediator Complex ; Nuclear Factor 90 Proteins ; Nuclear Proteins ; Nuclear Receptor Coactivator 2 ; Polycomb Repressive Complex 1 ; Prion Proteins ; Protein Aggregates ; Protein Domains ; Protein Tyrosine Phosphatases ; Solubility ; T-Cell Intracellular Antigen-1 ; Yeasts
Publicat a:	Scientific reports, Vol. 7 (2017) , art. 12134, ISSN 2045-2322

DOI: 10.1038/s41598-017-09714-z
PMID: 28935930

16 p, 9.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
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