3nve
From Proteopedia
MMHFGN segment 138-143 from Syrian Hamster prion
Structural highlights
Disease[PRIO_MESAU] Note=Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc. Function[PRIO_MESAU] May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).[1] Publication Abstract from PubMedPrion represents a unique class of pathogens devoid of nucleic acid. The deadly diseases transmitted by it between members of one species and, in certain instances to members of other species, present a public health concern. Transmissibility and the barriers to transmission between species have been suggested to arise from the degree to which a pathological protein conformation from an individual of one species can seed a pathological conformation in another species. However, this hypothesis has never been illustrated at an atomic level. Here we present three X-ray atomic structures of the same segment from human, mouse, and hamster PrP, which is critical for forming amyloid and confers species specificity in PrP seeding experiments. The structures reveal that different sequences encode different steric zippers and suggest that the degree of dissimilarity of these zipper structures gives rise to transmission barriers in prion disease, such as those that protect humans from acquiring bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD). Atomic structures suggest determinants of transmission barriers in mammalian prion disease.,Apostol MI, Wiltzius JJ, Sawaya MR, Cascio D, Eisenberg D Biochemistry. 2011 Feb 16. PMID:21323366[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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