Cryptic amyloidogenic regions in intrinsically disordered proteins

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 implica...

ver descrição completa

Detalhes bibliográficos
Autores: Santos Suárez, Jaime|||0000-0001-9045-7765, Pallarès i Goitiz, Irantzu|||0000-0002-8205-2060, Iglesias, Valentin|||0000-0002-6133-0869, Ventura, Salvador|||0000-0002-9652-6351
Tipo de documento: artigo
Data de publicação:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:249573
Acesso em linha:https://ddd.uab.cat/record/249573
https://dx.doi.org/urn:doi:10.1016/j.csbj.2021.07.019
Access Level:Acceso aberto
Palavra-chave: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
Descrição
Resumo: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.