Condition-dependent structural collapse in the intrinsically disordered N-terminal domain of prion protein.
N-terminal
intrinsically disordered
prion
structural collapse
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
25
06
2021
received:
18
05
2021
accepted:
27
06
2021
pubmed:
22
7
2021
medline:
23
7
2022
entrez:
21
7
2021
Statut:
ppublish
Résumé
Prion protein is composed of a structure-unsolved N-terminal domain and a globular C-terminal domain. Under limited trypsin digestion, mouse recombinant prion protein can be cleaved into two parts at residue Lys105. Here, we termed these two fragments as the N-domain (sequence 23-105) and the C-domain (sequence 106-230). In this study, the structural properties of the N-domain, the C-domain, and the full-length protein were explored using small-angle X-ray scattering, analytical ultracentrifugation, circular dichroism spectroscopy, and the 8-anilino-1-naphthalenesulfonic acid binding assay. The conformation and size of the prion protein were found to change sensitively under the solvent conditions. The positive residues in the sequence 23-99 of the N-domain were found to be responsible for the enhanced flexibility with the salt concentration reduced below 5 mM. The C-domain containing a hydrophobic patch tends to unfold and aggregate during a salt-induced structural collapse. The N-domain collapsed together with the C-domain at pH 5.2, whereas it collapsed independently at pH 4.2. The positively charged cluster (sequence 100-105) in the N-domain contributed to protecting the exposed hydrophobic surface of the C-domain.
Substances chimiques
Intrinsically Disordered Proteins
0
Prion Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
780-793Subventions
Organisme : Academia Sinica
Informations de copyright
© 2021 International Union of Biochemistry and Molecular Biology.
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