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The seesaw between normal function and protein aggregation: How functional interactions may increase protein solubility
Author(s) -
Temussi Piero Andrea,
Tartaglia Gian Gaetano,
Pastore Annalisa
Publication year - 2021
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.202100031
Subject(s) - protein aggregation , generality , corollary , function (biology) , protein folding , computational biology , biology , protein function , evolutionary biology , microbiology and biotechnology , biochemistry , economics , mathematics , pure mathematics , management , gene
Protein aggregation has been studied for at least 3 decades, and many of the principles that regulate this event are relatively well understood. Here, however, we present a different perspective to explain why proteins aggregate: we argue that aggregation may occur as a side‐effect of the lack of one or more natural partners that, under physiologic conditions, would act as chaperones. This would explain why the same surfaces that have evolved for functional purposes are also those that favour aggregation. In the course of reviewing this field, we substantiate our hypothesis with three paradigmatic examples that argue for the generality of our proposal. An obvious corollary of this hypothesis is, of course, that targeting the physiological partners of a protein could be the most direct and specific approach to designing anti‐aggregation molecules. Our analysis may thus inform a different strategy for combating diseases of protein aggregation and misfolding.