2ku5 | pdb_00002ku5
Mouse Prion Protein (121-231) with mutation D167S
Structural highlights
Disease[PRIO_MOUSE] 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_MOUSE] 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) (By similarity). 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.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe NMR structure of the horse (Equus caballus) cellular prion protein at 25 degrees C exhibits the typical PrP(C) [cellular form of prion protein (PrP)] global architecture, but in contrast to most other mammalian PrP(C)s, it contains a well-structured loop connecting the beta2 strand with the alpha2 helix. Comparison with designed variants of the mouse prion protein resulted in the identification of a single amino acid exchange within the loop, D167S, which correlates with the high structural order of this loop in the solution structure at 25 degrees C and is unique to the PrP sequences of equine species. The beta2-alpha2 loop and the alpha3 helix form a protein surface epitope that has been proposed to be the recognition area for a hypothetical chaperone, "protein X," which would promote conversion of PrP(C) into the disease-related scrapie form and thus mediate intermolecular interactions related to the transmission barrier for transmissible spongiform encephalopathies (TSEs) between different species. The present results are evaluated in light of recent indications from in vivo experiments that the local beta2-alpha2 loop structure affects the susceptibility of transgenic mice to TSEs and the fact that there are no reports on TSE in horses. Horse prion protein NMR structure and comparisons with related variants of the mouse prion protein.,Perez DR, Damberger FF, Wuthrich K J Mol Biol. 2010 Jul 9;400(2):121-8. Epub 2010 May 8. PMID:20460128[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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