Structural Analysis of the Quaking Homodimerization Interface

JOURNAL OF MOLECULAR BIOLOGY

卷:423

Article

Beuck, Christine^1,2  Qu, Song^1,2  Fagg, W. Samuel³  Ares, Manuel, Jr.³  Williamson, James R.^1,2 

[1] Scripps Res Inst, Dept Chem, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA

关键词: STAR/GSG proteins;    Qual domain;    crystal structure;    RNA binding;    C2C12 myoblasts;   

DOI  :  10.1016/j.jmb.2012.08.027

来源: Elsevier

【 摘 要 】

Quaking (QkI) is a prototypical member of the STAR (signal transducer and activator of RNA) protein family, which plays key roles in posttranscriptional gene regulation by controlling inRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences; however, the structural and functional roles of homodimerization and heterodimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 (germ line development defective-1) and Sam68 (Src-associated protein during mitosis, 68 kDa) but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels and impair QkI function in a splicing assay in vivo. Together, our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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