Amino Acids & Proteins MCAT Practice Question
A 68-year-old man presents with progressive dementia, ataxia, and myoclonus over the past 8 months. MRI shows characteristic spongiform changes in the cerebral cortex and basal ganglia. CSF analysis reveals elevated 14-3-3 protein. A diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is suspected. The pathophysiology of CJD involves conversion of the normal cellular prion protein (PrP^C), which is predominantly alpha-helical, into the pathogenic scrapie form (PrP^Sc), which is predominantly beta-sheet. Which of the following best explains why this conformational change leads to progressive neurodegeneration in prion diseases?
Answer choices
- AThe beta-sheet structure allows PrP^Sc to be readily cleaved by cellular proteases, generating toxic peptide fragments that trigger apoptosis
- CThe structural transition creates exposed hydrophobic regions that promote self-templating aggregation and protease resistance, allowing accumulation of insoluble depositsCorrect answer
- EThe conformational change introduces disulfide bond formation that cross-links PrP^Sc dimers, which are recognized and eliminated by the proteasome
- BThe increased alpha-helicity of PrP^Sc enhances binding to neuronal cell surface receptors, causing excitotoxic calcium influx
- DThe beta-sheet conformation restores normal cellular prion protein function but increases its expression 100-fold, overwhelming cellular quality control mechanisms
- FThe shift from alpha-helix to beta-sheet causes loss of the signal peptide, preventing normal ER translocation and triggering unfolded protein response-mediated neuronal death
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