Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes.
Intrinsically Disordered Proteins
/ chemistry
Kinetics
Magnetic Resonance Spectroscopy
Molecular Chaperones
/ chemistry
Molecular Dynamics Simulation
Polyelectrolytes
/ chemistry
Protein Binding
Protein Interaction Domains and Motifs
Protein Precursors
/ chemistry
Staining and Labeling
Thymosin
/ analogs & derivatives
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 11 2020
12 11 2020
Historique:
received:
21
07
2020
accepted:
14
09
2020
entrez:
13
11
2020
pubmed:
14
11
2020
medline:
1
12
2020
Statut:
epublish
Résumé
Highly charged intrinsically disordered proteins can form complexes with very high affinity in which both binding partners fully retain their disorder and dynamics, exemplified by the positively charged linker histone H1.0 and its chaperone, the negatively charged prothymosin α. Their interaction exhibits another surprising feature: The association/dissociation kinetics switch from slow two-state-like exchange at low protein concentrations to fast exchange at higher, physiologically relevant concentrations. Here we show that this change in mechanism can be explained by the formation of transient ternary complexes favored at high protein concentrations that accelerate the exchange between bound and unbound populations by orders of magnitude. Molecular simulations show how the extreme disorder in such polyelectrolyte complexes facilitates (i) diffusion-limited binding, (ii) transient ternary complex formation, and (iii) fast exchange of monomers by competitive substitution, which together enable rapid kinetics. Biological polyelectrolytes thus have the potential to keep regulatory networks highly responsive even for interactions with extremely high affinities.
Identifiants
pubmed: 33184256
doi: 10.1038/s41467-020-18859-x
pii: 10.1038/s41467-020-18859-x
pmc: PMC7661507
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Molecular Chaperones
0
Polyelectrolytes
0
Protein Precursors
0
prothymosin alpha
0
Thymosin
61512-21-8
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5736Commentaires et corrections
Type : ErratumIn
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