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Expert
Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 8; Issue 8; 21 April 2006 Abstract
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Structural comparison of members of the human fragile X protein family, and their known interactors
Barbara Bardoni, Laetitia Davidovic, Mounia Bensaid and Edouard W. Khandjian
Figure 1. Structural comparison of members of the human fragile X protein family, and their known interactors. FMRP, the protein encoded by the fragile X mental retardation 1 gene, is the archetype of this small RNA-binding protein family; the related proteins FXR1P and FXR2P are encoded by the fragile-X-related genes 1 and 2, respectively. Vertical black bars indicate identical amino acids in the three proteins; horizontal red lines show divergent amino acid regions in FXR1P and FXR2P as compared with FMRP. The KH boxes and the RGG domain, which are motifs found in most RNA-binding proteins, as well as the nuclear localisation and export signals (NLS and NES), are conserved in the three proteins. (The KH domain was originally identified in the protein K associated with a heterogeneous nuclear RNP, hence KH for ‘K Homologous’, whereas the RGG box is a common domain rich in arginine (R) and glycine (G) residues that confer a positive charge with high affinity for negatively charged RNA molecules.) The phosphorylation domain (PhD) contains several serine amino acids that can be phosphorylated, and this post-translational modification can modulate the properties of the protein. Proteins that directly interact with FMRP (and its related proteins) (Ref. 15) are shown in green circles below the protein–protein interaction domain (PPID), whereas the recently documented ‘RNA-kissing complex’ (Ref. 76) and the G-quartet RNA structure (Refs 42, 43) that bind to FMRP are shown in blue. The RNA-kissing complex refers to a specific motif that presents a loop–loop pseudoknot, whereas the G-quartet is a secondary structure within an mRNA in which four guanines form hydrogen bonds in a symmetrical square planar layer; thus FMRP might recognise RNA structures rather than purely a sequence. Abbreviations: aa, amino acids; CYFIP1/2, cytoplasmic FMRP-interacting protein 1/2; 82-FIP, 82 kDa FMRP-interacting protein; NUFIP1, nuclear FMRP-interacting protein 1.
| References cited
in Figure 1
15 Bardoni, B. and Mandel, J.L. (2002) Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes. Curr Opin Genet Dev 12, 284-293, PubMed 42 Darnell, J.C. et al. (2001) Fragile X mental retardation protein targets G quartet mRNAs important for neuronal function. Cell 107, 489-499, PubMed 43 Schaeffer, C. et al. (2001) The fragile X mental retardation protein binds specifically to its mRNA via a purine quartet motif. Embo J 20, 4803-4813, PubMed 76 Darnell, J.C. et al. (2005) Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. Genes Dev 19, 903-918, PubMed |
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