1g04
From Proteopedia
SOLUTION STRUCTURE OF SYNTHETIC 26-MER PEPTIDE CONTAINING 145-169 SHEEP PRION PROTEIN SEGMENT AND C-TERMINAL CYSTEINE
Structural highlights
Disease[PRIO_SHEEP] Note=Polymorphism at position 171 may be related to the alleles of scrapie incubation-control (SIC) gene in this species. 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. Note=Scrapie is a transmissible neurodegenerative disorder of sheep and goats. Most sheep that contract the disease naturally die between 24 and 50 months of age. The incubation period in sheep depends on the strain(s) of the infecting pathogen, sheep age at exposure, and the sheep genotype. The survival time is mainly determined by a single genetic locus, SIP, which has two alleles, susceptible (sa) and resistant (pa). Short incubation period is conferred by the partially dominant sa allele. Scrapie can be spread between flockmates, or it can be transmitted from an infected ewe to its lamb. Function[PRIO_SHEEP] 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). Publication Abstract from PubMedAccording to the "protein only" hypothesis, a conformational conversion of the non-pathogenic "cellular" prion isoform into a pathogenic "scrapie" isoform is the fundamental event in the onset of prion diseases. During this pathogenic conversion, helix H1 and two adjacent surface loops L2 and L3 of the normal prion protein are thought to undergo a conformational transition into an extended beta-like structure, which is prompted by interactions with the pre-existing beta-sheet. To get more insight into the interaction between the helix and one of the beta-strands in the partially unfolded prion protein, the solution structure of a synthetic linear peptide spanning helix H1 and beta-strand S2 (residues 142-166 in human numbering) was studied by circular dichroism and nuclear magnetic resonance spectroscopies. We found that, in contrast to many prion fragments studied earlier, this peptide (i) is highly soluble and does not aggregate up to a millimolar concentration range in aqueous medium and (ii) exhibits an intrinsic propensity to a beta-hairpin like conformation at neutral pH. This beta-propensity can be one of the internal driving forces of the molecular rearrangement responsible for the pathogenic conversion of the prion protein. Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2 (residues 142-166) shows beta-hairpin structure in solution.,Kozin SA, Bertho G, Mazur AK, Rabesona H, Girault JP, Haertle T, Takahashi M, Debey P, Hoa GH J Biol Chem. 2001 Dec 7;276(49):46364-70. Epub 2001 Sep 27. PMID:11577109[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Bertho, G | Debey, P | Girault, J P | Haertle, T | Hoa, G Hui Bon | Kozin, S A | Mazur, A K | Rabesona, H | Takahashi, M | Beta hairpin | Prion | Unknown function
