The prion protein (PrP) is currently one of the most studied molecules in the neurosciences. It is the main cause
of a group of neurological diseases collectively called transmissible spongiform encephalopathies that severely affect both
humans and a variety of mammals. Much effort has been directed to understanding the molecular basis of PrP activity,
both in physiological and pathological terms. In this context, identification of neuronally-relevant interactors of PrP may
play a crucial role. We recently discovered a specific, high-affinity (nanomolar KD) interaction with tyrosine hydroxylase
(TH), a enzyme catalyzing the rate-limiting step in the synthesis of the neurotransmitter dopamine. Using molecular
biological, biochemical and biophysical techniques we identified the C-terminal structured domain of PrP and the Nterminal
regulatory domain of TH as interacting domains between these two proteins. This interaction does not affect TH
activity in vitro, although co-expression experiments in HeLa and Chinese hamster ovary cells revealed that PrP is able to
internalize TH. Moreover, TH modulated the level of expression of PrP and its localization at the plasma membrane. This
novel interaction between two proteins of central importance in nervous system function may shed new light on our
understanding of PrP in neurological diseases.
Keywords: Prion, tyrosine hydroxylase, protein-protein interaction, surface plasmon resonance.
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