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 PubMed
Misfolded prion proteins are the cause of neurodegenerative diseases that affect many mammalian species, including humans. Transmission of the prion diseases poses a considerable public-health risk as a specific prion disease such as bovine spongiform encephalopathy can be transferred to humans and other mammalian species upon contaminant exposure. The underlying mechanism of prion propagation and the species barriers that control cross species transmission has been investigated quite extensively. So far a number of prion strains have been characterized and those have been intimately linked to species-specific infectivity and other pathophysiological manifestations. These strains are encoded by a protein-only agent, and have a high degree of sequence identity across mammalian species. The molecular events that lead to strain differentiation remain elusive. In order to contribute to the understanding of strain differentiation, we have determined the crystal structures of the globular, folded domains of four prion proteins (cow, deer, elk and Syrian hamster) bound to the POM1 antibody fragment Fab. Although the overall structural folds of the mammalian prion proteins remains extremely similar, there are several local structural variations observed in the misfolding-initiator motifs. In additional molecular dynamics simulation studies on these several prion proteins reveal differences in the local fluctuations and imply that these differences have possible roles in the unfolding of the globular domains. These local variations in the structured domains perpetuate diverse patterns of prion misfolding and possibly facilitate the strain selection and adaptation.
X-ray structural and molecular dynamical studies of the globular domains of cow, deer, elk and Syrian hamster prion proteins.,Baral PK, Swayampakula M, Aguzzi A, James MN J Struct Biol. 2015 Oct;192(1):37-47. doi: 10.1016/j.jsb.2015.08.014. Epub 2015, Aug 28. PMID:26320075[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Juanes ME, Elvira G, Garcia-Grande A, Calero M, Gasset M. Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation. J Biol Chem. 2009 Jan 30;284(5):2787-94. doi: 10.1074/jbc.M804051200. Epub 2008, Dec 5. PMID:19059915 doi:10.1074/jbc.M804051200
- ↑ Baral PK, Swayampakula M, Aguzzi A, James MN. X-ray structural and molecular dynamical studies of the globular domains of cow, deer, elk and Syrian hamster prion proteins. J Struct Biol. 2015 Oct;192(1):37-47. doi: 10.1016/j.jsb.2015.08.014. Epub 2015, Aug 28. PMID:26320075 doi:http://dx.doi.org/10.1016/j.jsb.2015.08.014
