2ymj | pdb_00002ymj
Solution structure of the QUA1 dimerization domain of pXqua, the Xenopus ortholog of Quaking.
Structural highlights
FunctionQKIA_XENLA RNA-binding protein that plays a central role in myelinization. Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence. Acts by regulating pre-mRNA splicing, mRNA export, mRNA stability and protein translation. Required to protect and promote stability of mRNAs which promotes oligodendrocyte differentiation. Participates in mRNA transport by regulating the nuclear export of MBP mRNA. Also involved in regulation of mRNA splicing of some pre-mRNA. Acts as a translational repressor (By similarity). Essential for notochord development.[1] Publication Abstract from PubMedThe 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 alpha-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. Solution structure of the QUA1 dimerization domain of pXqua, the Xenopus ortholog of Quaking.,Ali M, Broadhurst RW PLoS One. 2013;8(3):e57345. doi: 10.1371/journal.pone.0057345. Epub 2013 Mar 8. PMID:23520467[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
