User:Eliška Koutná/Sandbox 3
From Proteopedia
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= '''Prions''' = | = '''Prions''' = | ||
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
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| - | == '''General intro''' == | ||
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| - | Prion proteins are a common part of cell surface proteins in the mammalian nervous system, and they can, upon change of its conformation, become a highly infectious and pathogenic agent. The physiological form (PrPC) is encoded by the PRNP gene on chromosome 20 and when misfolded and aggregated, the pathological form (PrPSc) occurs, lacking any specific nucleic acid and its primary structure being determined by the PrPC form. When accumulated in the central nervous system (CNS) of mammals, PrPSc is known to be responsible for uprise of several untreatable progressive neurodegenerative diseases, generally called as transmissible spongiform encephalopathies (TSEs). These include kuru, fatal familial insomnia (FFI) and Creutzfeld-Jacob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, transmissible mink encephalopathy (TME) in mink, feline spongiform encephalopathy (FSE) in cat or chronic wasting disease (CWD) in deer and elk <ref>DOI 10.1186/1743-422X-8-493</ref>. | ||
== '''Protein structure''' == | == '''Protein structure''' == | ||
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The PrPSc differs from PrPC solely in conformation and is its isoform. The mature PrPC consists of approx. 208 amino acids, arranged as a disordered N-terminus and a globular C-terminal domain consisting of three α-helices and a short, antiparallel β-pleated sheet. <ref>DOI 10.1038/382180a0</ref> <ref>DOI 10.1073/pnas.97.1.145</ref>. There is a GPI membrane anchor at the C-terminus that tethers the protein to cell membranes and proteins that are secreted and lacking the anchor component has been proven to be unaffected by the infectious isoform <ref>DOI 10.1126/science.1110837</ref>. In contrast to the natural form of prion protein with only about 3 % of β-sheet secondary structure, the PrPSc form has about 47 % of the secondary structure in β-sheets <ref name="pan">DOI 10.1073/pnas.90.23.10962</ref> that create a core of four-rung β-solenoid fold <ref>DOI 10.3390/pathogens7010020</ref>. Accordingly, they also differ in their properties. PrPC is soluble, has a life-span between 2 and 4 hours, and is sensitive to proteolytic cleavage – when exposed to proteases, the protein is degraded completely <ref name="pan" />. The two most important cleavage events are the α cleavage which removes the unstructured N-terminal tail and leaves the globular domain attached to the cell membrane, and the cleavage on the C-terminal end (termed PrPC shedding) which releases PrPC into the extracellular space <ref name="sigurdson">DOI 10.3390/pathogens7010020</ref>. Under the same conditions, PrPSc is hydrolysed by proteases only partially by forming resistant core fragment PrP 27-30 <ref name="pan" />. In addition, it is insoluble in detergents and has a very long half-life, therefore accumulates in tissues easily. It has a tendency to form aggregates and fibrillar structures and is generally susceptible to oligomerization, whereas the PrPC form mainly exist as a monomer <ref name="cohen&prusiner">DOI 10.1146/annurev.biochem.67.1.793</ref>. Monomeric PrPSc has never been isolated. | The PrPSc differs from PrPC solely in conformation and is its isoform. The mature PrPC consists of approx. 208 amino acids, arranged as a disordered N-terminus and a globular C-terminal domain consisting of three α-helices and a short, antiparallel β-pleated sheet. <ref>DOI 10.1038/382180a0</ref> <ref>DOI 10.1073/pnas.97.1.145</ref>. There is a GPI membrane anchor at the C-terminus that tethers the protein to cell membranes and proteins that are secreted and lacking the anchor component has been proven to be unaffected by the infectious isoform <ref>DOI 10.1126/science.1110837</ref>. In contrast to the natural form of prion protein with only about 3 % of β-sheet secondary structure, the PrPSc form has about 47 % of the secondary structure in β-sheets <ref name="pan">DOI 10.1073/pnas.90.23.10962</ref> that create a core of four-rung β-solenoid fold <ref>DOI 10.3390/pathogens7010020</ref>. Accordingly, they also differ in their properties. PrPC is soluble, has a life-span between 2 and 4 hours, and is sensitive to proteolytic cleavage – when exposed to proteases, the protein is degraded completely <ref name="pan" />. The two most important cleavage events are the α cleavage which removes the unstructured N-terminal tail and leaves the globular domain attached to the cell membrane, and the cleavage on the C-terminal end (termed PrPC shedding) which releases PrPC into the extracellular space <ref name="sigurdson">DOI 10.3390/pathogens7010020</ref>. Under the same conditions, PrPSc is hydrolysed by proteases only partially by forming resistant core fragment PrP 27-30 <ref name="pan" />. In addition, it is insoluble in detergents and has a very long half-life, therefore accumulates in tissues easily. It has a tendency to form aggregates and fibrillar structures and is generally susceptible to oligomerization, whereas the PrPC form mainly exist as a monomer <ref name="cohen&prusiner">DOI 10.1146/annurev.biochem.67.1.793</ref>. Monomeric PrPSc has never been isolated. | ||
| - | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 14:48, 15 May 2019
Prions
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