Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes
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Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes. / Sottini, Andrea; Borgia, Alessandro; Borgia, Madeleine B.; Bugge, Katrine; Nettels, Daniel; Chowdhury, Aritra; Heidarsson, Pétur O.; Zosel, Franziska; Best, Robert B.; Kragelund, Birthe B.; Schuler, Benjamin.
I: Nature Communications, Bind 11, 5736, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Polyelectrolyte interactions enable rapid association and dissociation in high-affinity disordered protein complexes
AU - Sottini, Andrea
AU - Borgia, Alessandro
AU - Borgia, Madeleine B.
AU - Bugge, Katrine
AU - Nettels, Daniel
AU - Chowdhury, Aritra
AU - Heidarsson, Pétur O.
AU - Zosel, Franziska
AU - Best, Robert B.
AU - Kragelund, Birthe B.
AU - Schuler, Benjamin
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-020-18859-x
DO - 10.1038/s41467-020-18859-x
M3 - Journal article
C2 - 33184256
AN - SCOPUS:85095958053
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5736
ER -
ID: 252880791