title: Bioinformatical parsing of folding-on-binding proteins reveals their compositional and evolutionary sequence design.
abstract: Intrinsic disorder occurs when (part of) a protein remains unfolded during normal functioning. Intrinsically-disordered regions can contain segments that 'fold on binding' to another molecule. Here, we perform bioinformatical parsing of human 'folding-on-binding' (FB) proteins, into four subsets: Ordered regions, FB regions, Disordered regions that surround FB regions ('Disordered-around-FB'), and Other-Disordered regions. We examined the composition and evolutionary behaviour (across vertebrate orthologs) of these subsets. From a convergence of three separate analyses, we find that for hydrophobicity, Ordered regions segregate from the other subsets, but the Ordered and FB regions group together as highly conserved, and the Disordered-around-FB and Other-Disordered regions as less conserved (with a lesser significant difference between Ordered and FB regions). FB regions are highly-conserved with net positive charge, whereas Disordered-around-FB have net negative charge and are relatively less hydrophobic than FB regions. Indeed, these Disordered-around-FB regions are excessively hydrophilic compared to other disordered regions generally. We describe how our results point towards a possible compositionally-based steering mechanism of folding-on-binding.
authors.affiliation: Department of Biology, McGill University, Montreal, QC, Canada.
authors.forename: Mohanalakshmi
authors.initials: M
authors.lastname: Narasumani
authors.affiliation: Department of Biology, McGill University, Montreal, QC, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harrison
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology; D016208:Databases, Factual; D019143:Evolution, Molecular; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; D044162:Parathyroid Hormone-Related Protein