Complete modeling of PrPc in the cis interaction employing novel transpeptidation

Abstract

The pathogenesis of prion diseases is initiated when the cellular prion protein (PrPC) is misfolded into the scrapie prion protein (PrPSc). PrPC is composed of two major domains, the N-terminal intrinsically disordered tail and the C-terminal globular domain. These domains interact with each other via a copper(II)-driven cis interaction. The proposed model of this tertiary structure is a Cu2+ ion coordinated to three histidines in the N-terminal tail and one histidine in the C-terminal domain. To test this hypothesis, the N-terminal tail of PrPC is segmentally 15N-isoptically labeled via transpeptidation by 7M sortase A enzyme.