title: 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.
authors: MRC National Institute for Medical Research, London, UK.
authors: Ljiljana
authors: L
authors: Sjekloća
authors: Kris
authors: K
authors: Pauwels
authors: Annalisa
authors: A
authors: Pastore
mesh_terms: D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003001:Cloning, Molecular; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1