A low resolution study of the ultrastructure of Fragile X related proteins

Ljiljana Sjekloća , Petr V Konarev , John Eccleston , Ian A Taylor , Dmitri I Svergun , Annalisa Pastore (1)

1 Molecular Structure

Fragile X related proteins form a family implicated in RNA metabolism. Their sequence is composed of conserved N-terminal and central regions which contain Tudor and KH domains and of a divergent C-terminus with motifs rich in Arg and Gly. The most interesting member of the family is probably FMRP, since absence or mutation of this protein in human causes fragile X syndrome, the most common cause of inherited mental retardation. Understanding the structural properties of FMRP is essential for correlating it to its functions. The structures of isolated domains of FMRP have been reported, but nothing is yet known about the spatial arrangement of the different modules, partly because of difficulties in producing both the full-length protein and its multi-domain fragments in quantities, purities and monodispersity amenable for structural studies. Here, we describe how we have produced overlapping recombinant fragments of human FMRP and its paralogues which encompass the evolutionary conserved region. We have studied their behaviour in solution by complementary biochemical and biophysical techniques, identified the regions which promote self-association and determined their overall 3D shape. Our study paves the way to further studies and rationalises the existing knowledge on the self-association properties of these proteins.

Mots clés: Life Sciences

Ljiljana Sjekloća, Petr V Konarev, John Eccleston, Ian A Taylor, Dmitri I Svergun, et al.. A low resolution study of the ultrastructure of Fragile X related proteins. Biochemical Journal, 2009, 419 (2), pp.347-357. ⟨10.1042/BJ20082197⟩. ⟨hal-00479125⟩