3NMR

Crystal Structure of CUGBP1 RRM1/2-RNA Complex

Summary for 3NMR

• Entry DOI: 10.2210/pdb3nmr/pdb
• Related: 3NNA 3NNC 3NNH
• Descriptor: CUGBP Elav-like family member 1, RNA (5'-R(*GP*UP*UP*GP*UP*UP*UP*UP*GP*UP*UP*U)-3') (3 entities in total)
• Functional Keywords: rrm, pre-mrna splicing, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: Q92879
• Total number of polymer chains: 2
• Total formula weight: 23972.93

Authors

Teplova, M.,Song, J.,Gaw, H.,Teplov, A.,Patel, D.J. (deposition date: 2010-06-22, release date: 2010-10-27, Last modification date: 2024-10-16)

Primary citation

Teplova, M.,Song, J.,Gaw, H.Y.,Teplov, A.,Patel, D.J.
Structural Insights into RNA Recognition by the Alternate-Splicing Regulator CUG-Binding Protein 1.
Structure, 18:1364-1377, 2010

PubMed Abstract: CUG-binding protein 1 (CUGBP1) regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of myotonic dystrophy. CUGBP1 harbors three RRM domains and preferentially targets UGU-rich mRNA elements. We describe crystal structures of CUGBP1 RRM1 and tandem RRM1/2 domains bound to RNAs containing tandem UGU(U/G) elements. Both RRM1 in RRM1-RNA and RRM2 in RRM1/2-RNA complexes use similar principles to target UGU(U/G) elements, with recognition mediated by face-to-edge stacking and water-mediated hydrogen-bonding networks. The UG step adopts a left-handed Z-RNA conformation, with the syn guanine recognized through Hoogsteen edge-protein backbone hydrogen-bonding interactions. NMR studies on the RRM1/2-RNA complex establish that both RRM domains target tandem UGUU motifs in solution, whereas filter-binding assays identify a preference for recognition of GU over AU or GC steps. We discuss the implications of CUGBP1-mediated targeting and sequestration of UGU(U/G) elements on pre-mRNA alternative-splicing regulation, translational regulation, and mRNA decay.

PubMed: 20947024
DOI: 10.1016/j.str.2010.06.018

Experimental method

X-RAY DIFFRACTION (1.85 Å)