Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome
| Autor: | H A, Lewis, K, Musunuru, K B, Jensen, C, Edo, H, Chen, R B, Darnell, S K, Burley |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Binding Sites Sequence Homology Amino Acid Amino Acid Motifs Molecular Sequence Data RNA-Binding Proteins Nerve Tissue Proteins Crystallography X-Ray Autoantigens Protein Structure Tertiary Heterogeneous-Nuclear Ribonucleoprotein K Ribonucleoproteins Antigens Neoplasm Fragile X Syndrome Neuro-Oncological Ventral Antigen Amino Acid Sequence Paraneoplastic Syndromes Nervous System |
| Zdroj: | Cell. 100(3) |
| ISSN: | 0092-8674 |
| Popis: | The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 A resolution. Mammalian Nova antigens (1 and 2) constitute an important family of regulators of RNA metabolism in neurons, first identified using sera from cancer patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition is supported by an aliphatic alpha helix/beta sheet RNA-binding platform, which mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with 5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation results from perturbation of RNA binding by the FMR1 protein. |
| Databáze: | OpenAIRE |
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