Characterization of the self-interaction of polyglutamine binding protein 1

Polyglutamine binding protein 1, PQBP1, has been implicated in a number of neurodegenerative diseases, including Huntington's, Kennedy's, and Spinocerebellar Ataxia. It binds to the expanded polyglutamine tract that is the genetic hallmark of the nine recognized polyglutamine diseases. Though PQBP1 has been shown to localize to the nucleus and form intraneuronal aggregates, little is known about the structure or morphology of these aggregates. A combinatorial approach including proteomics, circular dichroism, and fluorescence spectroscopy has been employed to study the secondary structure, globular nature, and aggregation of PQBP1. Induced aggregation of recombinant PQBP1 revealed an amyloid morphology, like the plaques seen in Huntington's and Alzheimer's diseases. Though two binding domains exist in PQBP1 that were potential initiators of amyloid plaque formation, a comparative fluorescence analysis between isolated domains and the full protein implicated the N-terminal WW domain in nucleating the formation of amyloid protofibrils.