TY - JOUR T1 - Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases A1 - Castillo, Virginia A1 - Ventura, Salvador Y1 - 2009/08/21 N2 - Author Summary The aggregation of proteins in tissues is associated with the pathogenesis of more than 40 human diseases. The polypeptides underlying disorders such as Alzheimer's and Parkinson's are devoid of any regular structure, whereas the polypeptides causing familial amyotrophic lateral sclerosis or nonneuropathic systemic amyloidosis correspond to globular proteins. Little is known about the mechanism by which globular proteins under physiological conditions aggregate from their initially folded and soluble conformations. Interestingly, several of these pathogenic proteins display quaternary structure or are bound to other proteins in their physiological context. In the present work, we show that protein-protein interaction surfaces and regions with high aggregation propensity significantly overlap in these polypeptides. This suggests that the formation of native complexes and self-aggregation reactions probably compete in the cell, explaining why point mutations affecting the interface or the stability of the protein complex lead in many cases to the formation of toxic aggregates. This study proposes general strategies to fight against diseases associated with the deposition of globular polypeptides. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 8 UR - https://doi.org/10.1371/journal.pcbi.1000476 SP - e1000476 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000476 ER -