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CD230 or major prion protein (PrP)

Function: - neuroprotective adaptive cellular response to hypoxia [6] - prion protein PrPc (CD230) may be receptor for A4 oligomers; PrPc may bind & internalize A4 oligomers [8] Structure: - glypiated cell-surface glycoprotein - can occur in 2 structural conformations: a) PrPc (normal, of unknown function) C-terminal domain folded mostly in alpha-helical conformaion (3 alpha helices & a short antiparallel beta-sheet), stabilized by single disulfide bond linking helices 2 & 3 b) PrPSc (abnormal protein resulting in disease) PrPSc has high beta-sheet content Compartment: - associated with synaptic membranes Expression: - present in most mammalian tissues - highest levels in CNS - widely expressed in cells of immune system Pathology: - the PrPSc protein is extremely stable, resistant to proteolysis, organic solvents & high temperatures - once formed, it can initiate a chain reaction converting PrPc to the more stable PrPSc Polymorphism: - polymorphism at codon 129 in coding region of PrP gene (MM, VV, MV) & size of PrP fragment resistant to proteinase K digestion serves as classification for prion diseases Laboratory: Analysis: [2] 1) protein misfolding cyclic amplification (PMCA) 2) assay based upon selective binding to plasminogen 3) CSF real time quaking-induced conversion assay is the most sensitive & specific test for prion proteins in CSF [9]

Related

bovine spongiform encephalopathy; mad cow disease; BSE Creutzfeldt-Jakob [CJ] disease fatal familial insomnia Gerstmann-Straussler-Scheinker disease kuru prion prion gene protein misfolding cyclic amplification (PMCA) scrapie

General

glycoprotein plasma membrane protein

Properties

SIZE: MW = 28 kD entity length = 210 aa COMPARTMENT: plasma membrane MOTIF: consensus repeat (5) MOTIF-SEQUENCE: PHGGGWGQ specific amino acid-enriched region MOTIF: glycine residue (SEVERAL) alanine residue (SEVERAL) methionine residue {M129} cysteine residue {C179} MODIFICATION: cysteine residue {C214} N-glycosylation site {N181} N-glycosylation site {N197} cysteine residue {C214} MODIFICATION: cysteine residue {C179} glycosyl phosphatidylinositol [GPI] membrane anchor {C-TERMINUS}

Database Correlations

OMIM 176640 MORBIDMAP 176640 UniProt P04156 Entrez Gene 5621 Kegg hsa/hsa05060

References

  1. Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999
  2. Journal Watch 21(15):125, 2001 Saborio et al Nature 411:810, 2001 Maissen et al Lancet 357:2026, 2001
  3. Johnson & Gibbs NEJM 339:1994, 1998
  4. Coughey B. Trends in the Biochemical Sciences 26:235, 2001
  5. Entrez Gene :accession 5621
  6. McLennan NF et al, Prion protein accumulation and neuroprotection in hypoxic brain damage Am J Pathol 2004, 165:227 PMID: 15215178
  7. Sanchez-Juan P et al, CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease. Neurology 2006, 67:637 PMID: 16924018 - Collins SJ et al, Determinants of diagnostice investigation sensitivities across the clinical spectrum of sporadic Creutzfeldt-Jakob disease Brain 2006, 129:2278 PMID: 16816392 - Cali I et al, Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain 2006, 129:2266 PMID: 16923954
  8. Lauren J et al. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-oligomers. Nature 2009 Feb 26; 457:1128 PMID: 19242475 - Cisse M and Mucke L. Alzheimer's disease: A prion protein connection. Nature 2009 Feb 26; 457:1090. PMID: 19242462
  9. Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021