Web of Science: 43 cites, Scopus: 47 cites, Google Scholar: cites
Amyloidogenic regions and interaction surfaces overlap in globular proteins related to conformational diseases
Castillo Cano, Virginia (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Ventura i Zamora, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Data: 2009
Resum: Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins.
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. Creative Commons
Llengua: Anglès.
Document: article ; publishedVersion
Matèria: Protein structure ; Sequence assembly tools ; Protein interactions ; Polypeptides ; Globular proteins ; Antibodies ; Sequence analysis
Publicat a: PLOS Computational Biology, Vol. 5, Issue 8 (August 2009) , p. e1000476, ISSN 1553-734X

DOI: 10.1371/journal.pcbi.1000476
PMID: 19696882

16 p, 1.6 MB

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