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bioRxiv · 10.1101/211524

Interplay between folding and binding modulates protein sequences, structures, functions and regulation

Meszaros, B.·Dobson, L.·Ficho, E.·Tusnady, G. E.·Dosztanyi, Z.·Simon, I.
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Abstract

Intrinsically Disordered Proteins (IDPs) fulfill critical biological roles without having the potential to fold on their own. While lacking inherent structure, the majority of IDPs do reach a folded state via interaction with a protein partner, presenting a deep entanglement of the folding and binding process. Protein disorder has been recognized as a major determinant in several properties of proteins; yet the way the binding process is reflected in these features in general lacks this detail of description. Recent advances in database development enabled us to identify three basic scenarios of the interplay between folding and binding in unprecedented detail. These scenarios have fundamentally different properties in terms of protein sequence, structure, function and regulation, depending on the structural properties of the interacting partners. Strikingly, the existence of a binding partner and its structural properties influence all analyzed properties of proteins to the same extent as the divide between inherent order or disorder. The appreciation of this interplay between folding and binding is the basis for the successful charting of unknown territories in the protein interactome, the understanding of how different binding modes assemble regulatory networks, and the development of future pharmaceutical applications.

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Meszaros, B., Dobson, L., Ficho, E., Tusnady, G. E., Dosztanyi, Z., Simon, I.. 2017-10-30. Interplay between folding and binding modulates protein sequences, structures, functions and regulation. https://doi.org/10.1101/211524

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