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Role Of Protein Conformation

How can a protein such as PrP made by a cellular gene become an infectious agent? Prusiner and associates had found that PrP could exist in two forms, a normal or cellular form (PrPC) normally expressed at low levels in neurons and other cell types, and an abnormal or scrapie form (PrPSc) built up in diseased brain. PrPC is a cell-surface glycoprotein, the function of which has yet to be established. PrPC consists of a single polypeptide chain folded into predominantly spiral conformations known as α-helices. These structures give rise to a globular shape that is soluble and can be cleared from the cell by degrading enzymes called proteases.

In contrast, PrPSc that has been isolated from diseased brain is rich in an alternative conformation that resembles extended strands. These structures are known as β-sheets. The β-sheet rich PrPSc tends to aggregate and is resistant to heat and degradation by proteases. It is assumed that PrPSc can initiate the infection process by binding to predominantly-helical PrPC and converting it into more stable PrPSc with β-sheet conformation. This will set off a chain reaction leading to accumulation of large amounts of The illustration on the left is a computer-generated image of a healthy human prion protein. That on the right is a model of the disease-causing prion protein. The blue sections are β-strands, the green are α-helices, and the yellow are the chains connecting these regions. PrPSc to levels that result in brain tissue damage. The conformational conversion from α-helices to β-sheets transforms the benign PrPC into disease-causing PrPSc. This model of conformational conversion provides useful insights into the pathogenesis of prion diseases.

Additional topics

Medicine EncyclopediaGenetics in Medicine - Part 3Prion - A New Infectious Agent, Role Of Protein Conformation, Prion Diseases