Preformed structural elements feature in partner recognition by intrinsically unstructured proteins

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Abstract

Intrinsically unstructured proteins (IUPs) are devoid of extensive structural order but often display signs of local and limited residual structure. To explain their effective functioning, we reasoned that such residual structure can be crucial in their interactions with their structured partner(s) in a way that preformed structural elements presage their final conformational state. To check this assumption, a database of 24 IUPs with known 3D structures in the bound state has been assembled and the distribution of secondary structure elements and backbone torsion angles have been analysed. The high proportion of residues in coil conformation and with φ, ψ angles in the disallowed regions of the Ramachandran map compared to the reference set of globular proteins shows that IUPs are not fully ordered even in their bound form. To probe the effect of partner proteins on IUP folding, inherent conformational preferences of IUP sequences have been assessed by secondary structure predictions using the GOR, ALB and PROF algorithms. The accuracy of predicting secondary structure elements of IUPs is similar to that of their partner proteins and is significantly higher than the corresponding values for random sequences. We propose that strong conformational preferences mark regions in IUPs (mostly helices), which correspond to their final structural state, while regions with weak conformational preferences represent flexible linkers between them. In our interpretation, preformed elements could serve as initial contact points, the binding of which facilitates the reeling of the flexible regions onto the template. This finding implies that IUPs draw a functional advantage from preformed structural elements, as they enable their facile, kinetically and energetically less demanding, interaction with their physiological partner.

Original languageEnglish
Pages (from-to)1015-1026
Number of pages12
JournalJournal of molecular biology
Volume338
Issue number5
DOIs
Publication statusPublished - May 14 2004

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Keywords

  • DSSP, dictionary of secondary structures of proteins
  • Disorder-to-order transition
  • Disordered protein
  • IUP, intrinsically unstructured protein
  • Induced folding
  • Molecular recognition
  • Natively unfolded protein
  • PDB, Protein Data Bank
  • SOV, segmental overlap

ASJC Scopus subject areas

  • Molecular Biology

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