Sequence and structure properties uncover the natural classification of protein complexes formed by intrinsically disordered proteins via mutual synergistic folding

Bálint Mészáros, László Dobson, Erzsébet Fichó, István Simon

Research output: Contribution to journalArticle

Abstract

Intrinsically disordered proteins mediate crucial biological functions through their interactions with other proteins. Mutual synergistic folding (MSF) occurs when all interacting proteins are disordered, folding into a stable structure in the course of the complex formation. In these cases, the folding and binding processes occur in parallel, lending the resulting structures uniquely heterogeneous features. Currently there are no dedicated classification approaches that take into account the particular biological and biophysical properties of MSF complexes. Here, we present a scalable clustering-based classification scheme, built on redundancy-filtered features that describe the sequence and structure properties of the complexes and the role of the interaction, which is directly responsible for structure formation. Using this approach, we define six major types of MSF complexes, corresponding to biologically meaningful groups. Hence, the presented method also shows that differences in binding strength, subcellular localization, and regulation are encoded in the sequence and structural properties of proteins. While current protein structure classification methods can also handle complex structures, we show that the developed scheme is fundamentally different, and since it takes into account defining features of MSF complexes, it serves as a better representation of structures arising through this specific interaction mode.

Original languageEnglish
Article number5460
JournalInternational journal of molecular sciences
Volume20
Issue number21
DOIs
Publication statusPublished - Nov 1 2019

Fingerprint

Intrinsically Disordered Proteins
folding
proteins
Proteins
Protein Folding
Cluster Analysis
Redundancy
Structural properties
interactions
redundancy

Keywords

  • Coupled folding and binding
  • Fold recognition
  • IDP
  • Intrinsically disordered protein
  • Mutual synergistic folding
  • Protein
  • Protein interaction
  • Structural analysis
  • Structure-based classification

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Sequence and structure properties uncover the natural classification of protein complexes formed by intrinsically disordered proteins via mutual synergistic folding. / Mészáros, Bálint; Dobson, László; Fichó, Erzsébet; Simon, István.

In: International journal of molecular sciences, Vol. 20, No. 21, 5460, 01.11.2019.

Research output: Contribution to journalArticle

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