Structural analysis of the quaking homodimerization interface

Christine Beuck, Song Qu, W. Samuel Fagg, Manuel Ares, James R. Williamson

Research output: Contribution to journalArticlepeer-review

Abstract

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 mRNA 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.

Original languageEnglish (US)
Pages (from-to)766-781
Number of pages16
JournalJournal of Molecular Biology
Volume423
Issue number5
DOIs
StatePublished - Nov 9 2012
Externally publishedYes

Keywords

  • C2C12 myoblasts
  • Qua1 domain
  • RNA binding
  • STAR/GSG proteins
  • crystal structure

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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