Protein-RNA and protein-protein recognition by dual KH1/2 domains of the neuronal splicing factor Nova-1.
Structure
; 19(7): 930-44, 2011 Jul 13.
Article
en En
| MEDLINE
| ID: mdl-21742260
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Precursores del ARN
/
Proteínas de Unión al ARN
/
Transmisión Sináptica
/
ARN Interferente Pequeño
/
Síndrome de Opsoclonía-Mioclonía
/
Antígenos de Neoplasias
/
Proteínas del Tejido Nervioso
/
Neuronas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos