2ANR

Crystal structure (II) of Nova-1 KH1/KH2 domain tandem with 25nt RNA hairpin

Summary for 2ANR

• Entry DOI: 10.2210/pdb2anr/pdb
• Related: 2ANN
• Descriptor: 5'-R(*CP*(5BU)P*CP*GP*CP*GP*GP*AP*UP*CP*AP*GP*UP*CP*AP*CP*CP*CP*AP*AP*GP*CP*GP*AP*G)-3', RNA-binding protein Nova-1, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: protein-rna complex, kh domain, hairpin, rna-binding protein-rna complex, rna-binding protein/rna
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 2
• Total formula weight: 27461.29

Authors

Malinina, L.,Teplova, M.,Musunuru, K.,Teplov, A.,Darnell, J.C.,Burley, S.K.,Darnell, R.B.,Patel, D.J. (deposition date: 2005-08-11, release date: 2006-10-24, Last modification date: 2024-10-30)

Primary citation

Teplova, M.,Malinina, L.,Darnell, J.C.,Song, J.,Lu, M.,Abagyan, R.,Musunuru, K.,Teplov, A.,Burley, S.K.,Darnell, R.B.,Patel, D.J.
Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1.
Structure, 19:930-944, 2011

PubMed 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.

PubMed: 21742260
DOI: 10.1016/j.str.2011.05.002

Experimental method

X-RAY DIFFRACTION (1.94 Å)