Sequential, Structural and Functional Properties of Protein Complexes Are Defined by How Folding and Binding Intertwine

Bálint Mészáros, László Dobson, Erzsébet Fichó, Gábor E. Tusnády, Zsuzsanna Dosztányi, István Simon

Research output: Contribution to journalArticle

2 Citations (Scopus)


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 processes. Protein disorder has been recognized as a major determinant in several properties of proteins, such as sequence, adopted structure upon binding and function. However, the way the binding process is reflected in these features in general lacks a detailed description. Here, we defined three categories of protein complexes depending on the unbound structural state of the interactors and analyzed them in detail. We found that strikingly, the properties of interactors in terms of sequence and adopted structure are defined not only by the intrinsic structural state of the protein itself but also to a comparable extent by the structural state of the binding partner. The three different types of interactions are also regulated through divergent molecular tactics of post-translational modifications. This not only widens the range of biologically relevant sequence and structure spaces defined by ordered proteins but also presents distinct molecular mechanisms compatible with specific biological processes, separately for each interaction type. The distinct attributes of different binding modes identified in this study can help to understand how various types of interactions serve as building blocks for the assembly of tightly regulated and highly intertwined regulatory networks.

Original languageEnglish
Pages (from-to)4408-4428
Number of pages21
JournalJournal of molecular biology
Issue number22
Publication statusPublished - Nov 8 2019


  • coupled folding and binding
  • intrinsically disordered proteins
  • mutual synergistic folding
  • protein–protein interactions
  • regulatory networks

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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