Cell. 2000 Feb 4;100(3):323-32.

Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome.

Lewis HA, Musunuru K, Jensen KB, Edo C, Chen H, Darnell RB, Burley SK.

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Laboratories of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.

Abstract

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.

PMID:: 10676814; [PubMed - indexed for MEDLINE]

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Crystal structures of Nova-1 and Nova-2 K-homology RNA-binding domains. [Structure. 1999]
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Structures reported by this article

Crystal Structure Of Nova-2 Kh3 K-Homology Rna-Binding Domain Bound To 20-Mer Rna Hairpin

PDB: 1EC6

Source: Homo sapiens, synthetic construct

Method: X-Ray Diffraction

Resolution: 2.4 Å

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