Prion Diseases

Source: Stanley Prusiner, Science 216, 1982; Nobel Prize 1997

Finding

Prion diseases (CJD, BSE, kuru, scrapie) are caused by misfolded proteins. The normal prion protein (PrP-C) has an alpha-helix conformation; the pathogenic form (PrP-Sc) is predominantly beta-sheet. Same amino acid sequence, different shape. The critical property: PrP-Sc acts as a template converting normal PrP-C into misfolded form. The misfolded protein propagates by imposing its structure on correctly folded neighbors. Unlike viruses, the prion carries only its shape — and that shape suffices. The disease is invariably fatal.

Properties Violated

Non-fabrication inverted — the prion IS fabrication that propagates. It produces structure (the misfolded conformation) where none should exist, and that fabricated structure is self-replicating.

Honesty violated at the molecular level — the prion has the same amino acid sequence as the normal protein. It “claims” to be the same molecule. The difference is conformational, not compositional — a lie of shape, not substance.

Alignment violated — the protein’s normal function is replaced by pathological propagation.

Proportion violated — a single misfolded protein catalyzes conversion of vast numbers of normal proteins. Exponential cascade from minimal initial event.

Connections

Status

Prusiner, Science 216, 1982; PNAS 95, 1998. Structure: Pan et al., PNAS 90, 1993. The mapping is this project’s structural interpretation.


The mapping to the five properties is this project’s structural interpretation.