Structural and functional consequences of NEDD8 phosphorylation.
Allosteric Regulation
Amino Acid Sequence
Cloning, Molecular
Escherichia coli
/ genetics
Gene Expression
Genetic Vectors
/ chemistry
HEK293 Cells
HSP70 Heat-Shock Proteins
/ chemistry
Humans
Kinetics
NEDD8 Protein
/ chemistry
Phosphorylation
Protein Binding
Protein Interaction Mapping
Protein Processing, Post-Translational
Recombinant Proteins
/ chemistry
Sequence Alignment
Sequence Homology, Amino Acid
Substrate Specificity
Ubiquitin
/ chemistry
Ubiquitination
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 10 2021
12 10 2021
Historique:
received:
30
09
2020
accepted:
21
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
4
11
2021
Statut:
epublish
Résumé
Ubiquitin (Ub) and Ub-like proteins (Ubls) such as NEDD8 are best known for their function as covalent modifiers of other proteins but they are also themselves subject to post-translational modifications including phosphorylation. While functions of phosphorylated Ub (pUb) have been characterized, the consequences of Ubl phosphorylation remain unclear. Here we report that NEDD8 can be phosphorylated at S65 - the same site as Ub - and that S65 phosphorylation affects the structural dynamics of NEDD8 and Ub in a similar manner. While both pUb and phosphorylated NEDD8 (pNEDD8) can allosterically activate the Ub ligase Parkin, they have different protein interactomes that in turn are distinct from those of unmodified Ub and NEDD8. Among the preferential pNEDD8 interactors are HSP70 family members and we show that pNEDD8 stimulates HSP70 ATPase activity more pronouncedly than unmodified NEDD8. Our findings highlight the general importance of Ub/NEDD8 phosphorylation and support the notion that the function of pUb/pNEDD8 does not require their covalent attachment to other proteins.
Identifiants
pubmed: 34642328
doi: 10.1038/s41467-021-26189-9
pii: 10.1038/s41467-021-26189-9
pmc: PMC9020517
doi:
Substances chimiques
HSP70 Heat-Shock Proteins
0
NEDD8 Protein
0
NEDD8 protein, human
0
Recombinant Proteins
0
Ubiquitin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5939Informations de copyright
© 2021. The Author(s).
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