Uncovering the universality of self-replication in protein aggregation and its link to disease.

ABSTRACT: Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-growth mechanism, from those associated with disease, over those whose aggregates fulfill functional roles in biology, to those that aggregate only under artificial conditions. We find that, essentially, all such systems, regardless of their biological role, are capable of self-replication. However, for aggregates that have evolved to fulfill a structural role, the rate of self-replication is too lo

SUBMITTER: Meisl G 

PROVIDER: S-EPMC9374340 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature