Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state

Karlsson, E.; Paissoni, C.; Erkelens, A.; Tehranizadeh, Z. A.; Sorgenfrei, F. A.; Andersson, E.; Ye, W.; Camilloni, C.; Jemth, P.

doi:10.1101/2020.03.27.012328

bioRxiv · 10.1101/2020.03.27.012328

Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state

Karlsson, E.·Paissoni, C.·Erkelens, A.·Tehranizadeh, Z. A.·Sorgenfrei, F. A.·Andersson, E.·Ye, W.·Camilloni, C.·Jemth, P.

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Abstract

Intrinsically disordered protein (IDP) domains often have multiple binding partners. Little is known regarding molecular changes in the binding mechanism when a new interaction evolves from low to high affinity. Here we compared the degree of native contacts in the transition state of the interaction of two IDP domains, low-affinity ancestral and high-affinity human NCBD and CID. We found that the coupled binding and folding mechanism of the domains is overall similar, but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex while more heterogenous transient interactions, including electrostatic, and an increased disorder characterize the human complex. From an evolutionary perspective, adaptation to new binding partners for IDPs may benefit from this ability to exploit multiple alternative transient interactions while retaining the overall pathway.

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Karlsson, E., Paissoni, C., Erkelens, A., Tehranizadeh, Z. A., Sorgenfrei, F. A., Andersson, E., Ye, W., Camilloni, C., Jemth, P.. 2020-03-29. Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state. https://doi.org/10.1101/2020.03.27.012328

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