Two negatively charged invariant residues influence ligand binding and conformational dynamics of 14-3-3ζ.
14-3-3 protein
conformational change
fluorescence anisotropy
limited trypsinolysis
peptide interaction
surface plasmon resonance
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
25
07
2019
revised:
27
09
2019
accepted:
11
10
2019
pubmed:
7
11
2019
medline:
6
10
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
14-3-3 proteins bind and modulate the activities of a wide variety of phosphoproteins. Crystal structures of 14-3-3 isoforms bound to phospholigands have identified several residues important for ligand binding. Here, we report the role of two invariant residues, D124 and E131, in peptide binding and peptide-induced conformational changes of the binding pocket. Surprisingly, the D124A mutation abrogates peptide binding, while the E131A mutation results in a twofold increase in peptide affinity. The mutants are less stable than the wild-type protein, and peptide binding restores native-like stability to the E131A mutant. This reversibility is lost in the more open structure of D124A. Based on these results, we infer that E131 is a regulator of protein plasticity and D124 is the guardian of the active site geometry.
Identifiants
pubmed: 31693753
doi: 10.1002/1873-3468.13662
doi:
Substances chimiques
14-3-3 Proteins
0
Ligands
0
YWHAZ protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
878-886Informations de copyright
© 2019 Federation of European Biochemical Societies.
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