Detection of an interaction between prion protein and neuregulin I-β1 by fluorescence resonance energy transfer analysis

Abstract

Cellular prion protein (PrP) copurifies with neuregulin type I-β1 (NRG I-β1), but no interaction has been detected by a general immunoprecipitation study. We speculate that PrP interacts with NRG I-β1. Here, the interaction of PrP with NRG I-β1 was detected by measuring fluorescence resonance energy transfer (FRET) between enhanced blue (EBFP) and enhanced green (EGFP) fluorescent protein-fusion proteins. Full-length PrP interacted with EGFP in addition to NRG I-β1. From this result, we deduced that PrP interacts with EGFP through its unstructured N-terminal domain. We therefore detected FRET between PrP deleting the N-terminal domain and NRG I-β1. In contrast, the C-terminal domain of PrP interacted with NRG I-β1 and the proteins dissociated completely in the presence of sodium chloride. This interaction occurs at the nanomolar level, which is important for the reaction to be functional in organisms. We concluded that PrP interacted with NRG I-β1 through its C-terminal domain.

Graphical abstract

FRET analysis detected that the C-terminal domain of PrP interacted with NRG I-β1.

Key words:

• coreceptor
• fluorescence resonance energy transfer
• interaction
• neuregulin
• prion protein

Acknowledgment

We thank Ms Toshie Kuwahara for her technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan [grant number 17710188].