Cryptic amyloidogenic regions in intrinsically disordered proteins : Function and disease association
Santos, Jaime (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Pallarès i Goitiz, Irantzu (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Iglesias, Valentin (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2021
Abstract:	The amyloid conformation is considered a fundamental state of proteins and the propensity to populate it a generic property of polypeptides. Multiple proteome-wide analyses addressed the presence of amyloidogenic regions in proteins, nurturing our understanding of their nature and biological implications. However, these analyses focused on highly aggregation-prone and hydrophobic stretches that are only marginally found in intrinsically disordered regions (IDRs). Here, we explore the prevalence of cryptic amyloidogenic regions (CARs) of polar nature in IDRs. CARs are widespread in IDRs and associated with IDPs function, with particular involvement in protein-protein interactions, but their presence is also connected to a risk of malfunction. By exploring this function/malfunction dichotomy, we speculate that ancestral CARs might have evolved into functional interacting regions playing a significant role in protein evolution at the origins of life.
Grants:	Ministerio de Economía y Competitividad BIO2016-78310-R Ministerio de Ciencia e Innovación FPU17/01157
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amyloid ; Aggregation ; Protein disorder ; Intrinsically disordered proteins ; Protein-protein interactions ; Evolution ; APR, Aggregation-prone region ; CARs, Cryptic amyloidogenic regions ; CD, Circular dichroism ; CR, Congo red ; FTIR, Fourier transform infrared ; IDPs, Intrinsically disordered proteins ; IDRs, Intrinsically disordered regions ; PBS, Phosphate buffer saline ; PPI, Protein-protein interactions ; TEM, Transmission electron microscopy ; Th-T, Thioflavin-T ; Rb, Retinoblastoma associated proteins ; RbC, Core region of Rb
Published in:	Computational and Structural Biotechnology Journal, Vol. 19 (July 2021) , p. 4192-4206, ISSN 2001-0370

DOI: 10.1016/j.csbj.2021.07.019
PMID: 34527192

15 p, 2.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles