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.
Highlights
Many intrinsically disordered proteins (IDPs)/IDP regions (IDPRs) possess an exceptional binding promiscuity often associated with the ability to fold in a template dependent manner, where a single IDPR can bind to multiple partners gaining very different structures in the bound state [28,44]
We looked at the entire amino acid sequences of these proteins to see where the most frequent single nucleotide polymorphisms (SNPs) occurred
We identified the conserved amino acid sequences within the binding sites of the protein-protein interactions, as well as any mutations, single nucleotide polymorphisms (SNPs), and intrinsically disordered protein regions (IDPRs) related to the dystrophinassociated protein complex (DAPC) proteins
Summary
It is recognized that many biologically active proteins, known as intrinsically disordered proteins (IDPs), lack stable tertiary and/or secondary structure under physiological conditions in vitro [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. We identified the conserved amino acid sequences within the binding sites of the protein-protein interactions, as well as any mutations, single nucleotide polymorphisms (SNPs), and intrinsically disordered protein regions (IDPRs) related to the DAPC proteins.
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