FIGURE 17.30 Viroids Replicate by a Rolling Circle Mechanism

Two rounds of rolling circle replication are used by viroids to replicate themselves. Upon entry into a plant cell, the circular, positive ssRNA uses the plant RNA polymerase to make a minus strand. The polymerase continues to make multiple copies using the rolling circle mechanism. The linear, negative ssRNA uses its own catalytic activity to cut itself into genome-sized units that are circularized. The circular, negative ssRNA then undergoes another round of rolling circle replication and self-cleavage to produce multiple copies of the linear plus strand. Finally these are circularized to give the infectious circular, positive ssRNA form.

Prion proteins exist in two alternative forms. The pathogenic form provokes the normal form to change conformation so making more of the pathogenic version.

rearranges to produce the pathological form of the protein (scrapie PrP or PrPSc), which then polymerizes to form fibrillar aggregates. The prion protein is not chemically altered; it merely changes shape. Healthy prions consist largely of a-helical segments, whereas rogue prions have less a-helix and lots of b-sheet regions instead. PrPC is estimated to have 42% a-helix and 3% b-sheet whereas PrPSc has 30% a-helix and 43% b-sheet (see Ch. 7 for protein structures). The presence of the misfolded PrPSc form induces the normal PrPC proteins to change conformation also (Fig. 17.31). Thus, once a few molecules of PrPSc are present, they propagate themselves by catalyzing the conversion of PrPC to more of the PrPSc isoform. Precisely how these changes in protein conformation and aggregation damage nerve cells is still obscure. Nonetheless, once the change to the scrapie agent has been initiated, slow nervous degeneration and eventual death are inevitable.

Prion disease occurs by three mechanisms, all of which lead to a similar final result. In infectious prion disease, the pathological form of the prion protein is passed from

PrPSc (scrapie PrP) The pathological form of the prion protein, sometimes known as the scrapie agent

FIGURE 17.31 Re-Folding of Normal Prion is Triggered by Rogue Prion

Normal prions can be induced to change their conformation by contact with a misfolded prion. When the pathological misfolded form PrPsc comes in contact with the normal prion, PrPc, the normal alpha-helical structure is converted into beta-sheet. The alternate conformation has a tendency to aggregate, forming clumps that damage nerve cells.





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