On the aggregation properties of FMRP – a link with the FXTAS syndrome?

Authors


A. Pastore, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Fax: +44 20 8905 4477
Tel: +44 20 8816 2630
E-mail: apastor@nimr.mrc.ac.uk

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.

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