Heyam, Alex and Coupland, Claire E. and Degut, Clement and Haley, Ruth A. and Baxter, Nicola J. and Jakob, Leonhard and Aguiar, Pedro M. and Meister, Gunter and Williamson, Michael P. and Lagos, Dimitris and Plevin, Michael J. (2017) Conserved asymmetry underpins homodimerization of Dicer-associated double-stranded RNA-binding proteins. NUCLEIC ACIDS RESEARCH, 45 (21). pp. 12577-12584. ISSN 0305-1048, 1362-4962
Full text not available from this repository. (Request a copy)Abstract
Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs). In each case, the interaction involves a region of the protein that contains a Type B dsRBD. All three dsRBPs are reported to homodimerize, with the Dicer-binding region implicated in self-association. We report that these dsRBD homodimers display structural asymmetry and that this unusual self-association mechanism is conserved from flies to humans. We show that the core dsRBD is sufficient for homodimerization and that mutation of a conserved leucine residue abolishes self-association. We attribute differences in the self-association properties of Loqs, TRBP and PACT to divergence of the composition of the homodimerization interface. Modifications that make TRBP more like PACT enhance self-association. These data are examined in the context of miRNA biogenesis and the protein/protein interaction properties of Type B dsRBDs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MICRORNA BIOGENESIS; KINASE PKR; HUMAN TRBP; DOMAIN; PACT; ACTIVATION; COMPLEXES; INTERACTS; SYMMETRY; MODEL; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie > Prof. Dr. Dina Grohmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 20 Feb 2019 15:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1766 |
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