User:Eliška Koutná/Sandbox 3
From Proteopedia
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== '''Protein structure''' == | == '''Protein structure''' == | ||
| - | 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>PMID 10618385</ref><ref>DOI 10.1038/382180a0</ref>. | + | 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>PMID 10618385</ref><ref>DOI 10.1038/382180a0</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. |
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 14:57, 15 May 2019
Prions
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