title: 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).
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.
authors.affiliation: Protein Technology Core, Centre for Cellular and Molecular Platforms (C-CAMP), NCBS-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India.|Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX13QU, United Kingdom.
authors.forename: Muniasamy
authors.initials: M
authors.lastname: Neerathilingam
authors.affiliation: Protein Technology Core, Centre for Cellular and Molecular Platforms (C-CAMP), NCBS-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India.
authors.forename: Sneha G
authors.initials: SG
authors.lastname: Bairy
authors.affiliation: Protein Technology Core, Centre for Cellular and Molecular Platforms (C-CAMP), NCBS-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India.
authors.forename: Sumukh
authors.initials: S
authors.lastname: Mysore
mesh_terms: D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D051419:Paxillin / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D064267:Intrinsically Disordered Proteins; D051419:Paxillin; D010446:Peptide Fragments; D051416:Focal Adhesion Protein-Tyrosine Kinases