Deciphering Mode of Action of Functionally Important Regions in the Intrinsically Disordered Paxillin (Residues 1-313) Using Its Interaction with FAT (Focal Adhesion Targeting Domain of Focal Adhesion Kinase)

PLoS One. 2016 Feb 29;11(2):e0150153. doi: 10.1371/journal.pone.0150153. eCollection 2016.

Abstract

Intrinsically disordered proteins (IDPs) play a major role in various cellular functions ranging from transcription to cell migration. Mutations/modifications in such IDPs are shown to be associated with various diseases. Current strategies to study the mode of action and regulatory mechanisms of disordered proteins at the structural level are time consuming and challenging. Therefore, using simple and swift strategies for identifying functionally important regions in unstructured segments and understanding their underlying mechanisms is critical for many applications. Here we propose a simple strategy that employs dissection of human paxillin (residues 1-313) that comprises intrinsically disordered regions, followed by its interaction study using FAT (Focal adhesion targeting domain of focal adhesion kinase) as its binding partner to retrace structural behavior. Our findings show that the paxillin interaction with FAT exhibits a masking and unmasking effect by a putative intra-molecular regulatory region. This phenomenon suggests how cancer associated mutations in paxillin affect its interactions with Focal Adhesion Kinase (FAK). The strategy could be used to decipher the mode of regulations and identify functionally relevant constructs for other studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Focal Adhesion Protein-Tyrosine Kinases / chemistry*
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Focal Adhesions / metabolism*
  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / metabolism*
  • Models, Molecular
  • Paxillin / chemistry*
  • Paxillin / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Intrinsically Disordered Proteins
  • Paxillin
  • Peptide Fragments
  • Focal Adhesion Protein-Tyrosine Kinases

Grant support

This work was supported by the Department of Biotechnology, India [Award Number: BT/IN/FINLAND/29/MN/2013 Recipient: Muniasamy Neerathilingam, D.Phil (Oxford)]. The funding body does not have any role in the design of the research study and publication decision.