Summary information and primary citation

PDB-id
2ann; SNAP-derived features in text and JSON formats; DNAproDB
Class
RNA-binding protein-RNA
Method
X-ray (2.3 Å)
Summary
Crystal structure (i) of nova-1 kh1-kh2 domain tandem with 25 nt RNA hairpin
Reference
Teplova M, Malinina L, Darnell JC, Song J, Lu M, Abagyan R, Musunuru K, Teplov A, Burley SK, Darnell RB, Patel DJ (2011): "Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1." Structure, 19, 930-944. doi: 10.1016/j.str.2011.05.002.
Abstract
Nova onconeural antigens are neuron-specific RNA-binding proteins implicated in paraneoplastic opsoclonus-myoclonus-ataxia (POMA) syndrome. Nova harbors three K-homology (KH) motifs implicated in alternate splicing regulation of genes involved in inhibitory synaptic transmission. We report the crystal structure of the first two KH domains (KH1/2) of Nova-1 bound to an in vitro selected RNA hairpin, containing a UCAG-UCAC high-affinity binding site. Sequence-specific intermolecular contacts in the complex involve KH1 and the second UCAC repeat, with the RNA scaffold buttressed by interactions between repeats. Whereas the canonical RNA-binding surface of KH2 in the above complex engages in protein-protein interactions in the crystalline state, the individual KH2 domain can sequence-specifically target the UCAC RNA element in solution. The observed antiparallel alignment of KH1 and KH2 domains in the crystal structure of the complex generates a scaffold that could facilitate target pre-mRNA looping on Nova binding, thereby potentially explaining Nova's functional role in splicing regulation.

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