Probing TDP-43 condensation using an in silico designed aptamer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 06 2022
23 06 2022
Historique:
received:
05
10
2021
accepted:
23
05
2022
entrez:
23
6
2022
pubmed:
24
6
2022
medline:
28
6
2022
Statut:
epublish
Résumé
Aptamers are artificial oligonucleotides binding to specific molecular targets. They have a promising role in therapeutics and diagnostics but are often difficult to design. Here, we exploited the catRAPID algorithm to generate aptamers targeting TAR DNA-binding protein 43 (TDP-43), whose aggregation is associated with Amyotrophic Lateral Sclerosis. On the pathway to forming insoluble inclusions, TDP-43 adopts a heterogeneous population of assemblies, many smaller than the diffraction-limit of light. We demonstrated that our aptamers bind TDP-43 and used the tightest interactor, Apt-1, as a probe to visualize TDP-43 condensates with super-resolution microscopy. At a resolution of 10 nanometers, we tracked TDP-43 oligomers undetectable by standard approaches. In cells, Apt-1 interacts with both diffuse and condensed forms of TDP-43, indicating that Apt-1 can be exploited to follow TDP-43 phase transition. The de novo generation of aptamers and their use for microscopy opens a new page to study protein condensation.
Identifiants
pubmed: 35739092
doi: 10.1038/s41467-022-30944-x
pii: 10.1038/s41467-022-30944-x
pmc: PMC9226187
doi:
Substances chimiques
DNA-Binding Proteins
0
Oligonucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3306Subventions
Organisme : Medical Research Council
ID : MC_EX_MR/N50192X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M010996/1
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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