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

被引:278
作者
Lewis, HA
Musunuru, K
Jensen, KB
Edo, C
Chen, H
Darnell, RB
Burley, SK
机构
[1] Rockefeller Univ, Labs Mol Biophys, New York, NY 10021 USA
[2] Rockefeller Univ, Mol Neurooncol Lab, New York, NY 10021 USA
[3] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
关键词
D O I
10.1016/S0092-8674(00)80668-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 Angstrom 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.
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收藏
页码:323 / 332
页数:10
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