On the aggregation properties of FMRP - A link with the FXTAS syndrome?

Abstract

Fragile X mental retardation protein (FMRP) is an RNA binding protein necessary for correct spatiotemporal control of neuronal gene expression in humans. Lack of functional FMRP causes fragile X mental retardation, which is the most common inherited neurodevelopmental disorder in humans. In a previous study, we described the biochemical and biophysical aggregation properties of constructs spanning the conserved region of FMRP and of two other human fragile X related (FXR) proteins, FXR1P and FXR2P. Here, we show that the same regions have an intrinsic tendency to aggregate and spontaneously misfold towards β-rich structures, also under non-destabilizing conditions. These findings pave the way to future studies of the mechanism of formation of FXR-containing ribonucleoprotein granules and suggest a possible link with the as yet poorly understood FXR proteins' associated pathologies. Structured digital abstract to by to by to by Lack of the Fragile X mental retardation protein (FMRP) causes an inherited mental retardation in humans. We describe here that constructs spanning the conserved N-terminus of FMRP and of the two homologues, FXR1P and FXR2P, have an intrinsic tendency to aggregate and misfold towards beta-rich structures, also under non-destabilizing conditions. These findings suggest a link with FMRP associated pathologies. © 2011 FEBS.