Prion

Prion：The GPI anchor sequence will anchor Prc to the outer surface of the plasmamembrane。

Prion

• PrP
  • structure
    • • PrPc
        • no beta sheets
        • 40% a-helixes
      • PrPsc
        • 50% beta sheet
        • 20% a-helixes
  • PrPc
    • Informatics
      • product of one gene
      • present in brain and many other tissue types
      • This shown is the processed form, a C terminal yellow ladder sequences is replaced by GPI anchor sequence during the processing.
        • The GPI anchor sequence will anchor Prc to the outer surface of the plasmamembrane
    • the PrPc knockout mice is resistence to all associated diseases
    • not resistent to proteolytic treatment.
    • Cellular biological function
      • the knock out mice shows more sensitivity to pressures.
      • PrPc is concentrated in both pre and post-synaptic membranes.
      • hypothesis 1
        • octomeric repeat region can binds 5 Cu2+ at synapses.
        • Cu2+ can catalysis the conversion of reactive oxygen species. (function like SOD)
      • hypothesis 2
        • PrPC bind Zn2+, and mediates Zn2+ transportation.
        • Zn2+'s location might be very important for the function of the brain.
  • PrPsc
    • can aggregates into amyloid fibril: a coil of several fibrils perpendicular to a cylindrical axis.
    • The proteolytic removal of 60 - 70 aa from the A-terminal can leaves the protein a protease-resistant core.
      • this is why eating PrPsc can cause vCJD
      • because PrPsc itself is resist to degestion
    • shows infectivity
      • infectivity is neutralized by denaturing agents and anti-PrP antibodies.
  • Propagation of PrPsc conformation
    • hypothesis 1: template-assisted conversion
    • hypothesis 2: Nucleation-polymerisation