Uncovering the universality of self-replication in protein aggregation and its link to disease
Author(s)
Type
Journal Article
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 low to be significant on the biologically relevant time scale. By contrast, all disease-related proteins are able to self-replicate quickly compared to the time scale of the associated disease. Our findings establish the ubiquity of self-replication and point to its potential importance across aggregation-related disorders.
Date Issued
2022-08-12
Date Acceptance
2022-06-28
Citation
Science Advances, 2022, 8 (32), pp.1-11
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
11
Journal / Book Title
Science Advances
Volume
8
Issue
32
Copyright Statement
Copyright © 2022
The Authors, some
rights reserved;
exclusive licensee
American Association
for the Advancement
of Science. No claim to
original U.S.Government
Works. Distributed
under a Creative
Commons Attribution
NonCommercial
License 4.0 (CC BY-NC).
The Authors, some
rights reserved;
exclusive licensee
American Association
for the Advancement
of Science. No claim to
original U.S.Government
Works. Distributed
under a Creative
Commons Attribution
NonCommercial
License 4.0 (CC BY-NC).
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000841491100014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
ALPHA-SYNUCLEIN
FIBRIL FORMATION
GELSOLIN CONCENTRATION
LAG PHASE
MEROZOITE SURFACE PROTEIN-2
Multidisciplinary Sciences
PHENOL-SOLUBLE MODULINS
PLASMODIUM-FALCIPARUM
POLYGLUTAMINE AGGREGATION
Science & Technology
Science & Technology - Other Topics
SECONDARY NUCLEATION
SICKLE HEMOGLOBIN POLYMERIZATION
Publication Status
Published
Article Number
ARTN eabn6831
Date Publish Online
2022-08-12