title: Ordered disorder of the astrocytic dystrophin-associated protein complex in the norm and pathology.
abstract: The abundance and potential functional roles of intrinsically disordered regions in aquaporin-4, Kir4.1, a dystrophin isoforms Dp71, α-1 syntrophin, and α-dystrobrevin; i.e., proteins constituting the functional core of the astrocytic dystrophin-associated protein complex (DAPC), are analyzed by a wealth of computational tools. The correlation between protein intrinsic disorder, single nucleotide polymorphisms (SNPs) and protein function is also studied together with the peculiarities of structural and functional conservation of these proteins. Our study revealed that the DAPC members are typical hybrid proteins that contain both ordered and intrinsically disordered regions. Both ordered and disordered regions are important for the stabilization of this complex. Many disordered binding regions of these five proteins are highly conserved among vertebrates. Conserved eukaryotic linear motifs and molecular recognition features found in the disordered regions of five protein constituting DAPC likely enhance protein-protein interactions that are required for the cellular functions of this complex. Curiously, the disorder-based binding regions are rarely affected by SNPs suggesting that these regions are crucial for the biological functions of their corresponding proteins.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
authors.forename: Insung
authors.initials: I
authors.lastname: Na
authors.forename: Derek
authors.initials: D
authors.lastname: Redmon
authors.forename: Markus
authors.initials: M
authors.lastname: Kopa
authors.forename: Yiru
authors.initials: Y
authors.lastname: Qin
authors.forename: Bin
authors.initials: B
authors.lastname: Xue
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000818:Animals; D002645:Chickens / Q000235:genetics* / Q000378:metabolism; D049028:Dystrophin-Associated Protein Complex / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008116:Lizards / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009137:Muscular Dystrophy, Animal; D020641:Polymorphism, Single Nucleotide; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014982:Xenopus laevis; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: D049028:Dystrophin-Associated Protein Complex