title: Abundance and functional roles of intrinsic disorder in the antimicrobial peptides of the NK-lysin family.
abstract: NK-lysins are antimicrobial peptides (AMPs) that participate in the innate immune response and also have several pivotal roles in various biological processes. Such multifunctionality is commonly found among intrinsically disordered proteins. However, NK-lysins have never been systematically analyzed for intrinsic disorder. To fill this gap, the amino acid sequences of NK-lysins from various species were collected from UniProt and used for the comprehensive computational analysis to evaluate the propensity of these proteins for intrinsic disorder and to investigate the potential roles of disordered regions in NK-lysin functions. We analyzed abundance and peculiarities of intrinsic disorder distribution in all-known NK-lysins and showed that many NK-lysins are expected to have substantial levels of intrinsic disorder. Curiously, high level of intrinsic disorder was also found even in two proteins with known 3D-strucutres (NK-lysin from pig and human granulysin). Many of the identified disordered regions can be involved in protein-protein interactions. In fact, NK-lysins are shown to contain three to eight molecular recognition features; i.e. short structure-prone segments which are located within the long disordered regions and have a potential to undergo a disorder-to-order transition upon binding to a partner. Furthermore, these disordered regions are expected to have several sites of various posttranslational modifications. Our study shows that NK-lysins, which are AMPs with a set of prominent roles in the innate immune response, are expected to abundantly possess intrinsically disordered regions that might be related to multifunctionality of these proteins in the signal transduction pathways controlling the host response to pathogenic agents.
authors.affiliation: a Faculty of Science, Department of Biological Sciences , University of Jeddah , Jeddah , Saudi Arabia.|b Department of Cell Biology, Genetic Engineering and Biotechnology Division , National Research Centre , P.O. Box 12622, Gizza , Egypt.
authors.forename: Haitham A
authors.initials: HA
authors.lastname: Yacoub
authors.affiliation: a Faculty of Science, Department of Biological Sciences , University of Jeddah , Jeddah , Saudi Arabia.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Al-Maghrabi
authors.affiliation: b Department of Cell Biology, Genetic Engineering and Biotechnology Division , National Research Centre , P.O. Box 12622, Gizza , Egypt.
authors.forename: Ekram S
authors.initials: ES
authors.lastname: Ahmed
authors.affiliation: c Faculty of Sciences, Department of Biological Sciences , King Abdulaziz University , P.O. Box 80203, Jeddah , Saudi Arabia.|d Laboratory of Structural Dynamics, Stability and Folding of Proteins , Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia.|e Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine , University of South Florida , Tampa , FL , USA.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology; D006801:Humans; D008958:Models, Molecular; D005810:Multigene Family; D011487:Protein Conformation; D011510:Proteolipids / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine
chemical_list: D000890:Anti-Infective Agents; D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; C093238:NK-lysin; D011510:Proteolipids
keywords: NK-lysin; antimicrobial peptide; granulysin; innate immune response; intrinsic disorder; intrinsically disordered proteins; prediction