The STAR protein family member Quaking is essential for early development in vertebrates. For example, in oligodendrocyte cells it regulates the splicing, localization, translation and lifetime of a set of mRNAs that code for crucial components of myelin. The Quaking protein contains three contiguous conserved regions: a QUA1 oligomerization element, followed by a single-stranded RNA binding motif comprising the KH and QUA2 domains. An embryonic lethal point mutation in the QUA1 domain, E48G, is known to affect both the aggregation state and RNA-binding properties of the murine Quaking ortholog (QKI). Here we report the NMR solution structure of the QUA1 domain from the Xenopus laevis Quaking ortholog (pXqua), which forms a dimer composed of two perpendicularly docked α-helical hairpin motifs. Size exclusion chromatography studies of a range of mutants demonstrate that the dimeric state of the pXqua QUA1 domain is stabilized by a network of interactions between side-chains, with significant roles played by an intra-molecular hydrogen bond between Y41 and E72 (the counterpart to QKI E48) and an inter-protomer salt bridge between E72 and R67. These results are compared with recent structural and mutagenesis studies of QUA1 domains from the STAR family members QKI, GLD-1 and Sam68.