Passage
Spinocerebellar ataxia 3 (SCA3) is a neurodegenerative disease that manifests as a progressive decrease in coordination of limbs and frequently results in impaired speech and eye coordination. It is associated with extension of the polyglutamine (polyQ) region of the ataxin-3 protein. The polyQ region is encoded by a series of consecutive CAG codons known as poly-CAG repeats. These regions vary in length from one person to another, ranging from as few as 10 to as many as 80 repeats. SCA3 has been reported in patients with polyQ regions exceeding ~55 repeats, and increased polyQ length correlates with earlier onset of the disease and greater clinical severity.Circular dichroism (CD) is a method of assessing protein secondary structure. It measures a molecule's ability to absorb left- and right-handed circularly polarized light of varying wavelengths. The absorption difference is known as "ellipticity," denoted by Δε. Alpha-helices have a maximum Δε at 190 nm, and beta-sheets have a maximum Δε at 200 nm.CD results show that as the length of the ataxin-3 polyQ region increases, alpha-helical nature is lost and the protein aggregates, ultimately precipitating out of solution and depositing in brain and other tissues. Furthermore, as proteins aggregate, they form beta-sheets. These beta-sheets are in the parallel orientation, and each sheet can interact with sheets in other proteins to form long, insoluble structures known as amyloid fibers (Figure 1) .
Figure 1 Depiction of the ataxin-3 polyQ region shifting from alpha-helical (cylinders) to beta-sheet (arrows) structure and aggregatingGlutamine can be encoded by both CAG and CAA codons. Researchers investigated survival rates in fruit flies expressing ataxin-3 with polyQ regions of equal length encoded by either CAG-CAG or CAA-CAG repeats (Table 1) . The protein products had identical amino acid sequences.Table 1 Fruit Fly Survival Rates Relative to Ataxin-3 Expression
Adapted from Bevivino AE, Loll PJ. An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils. Proc Natl Acad Sci USA. 2001;98(21) :11955-60.
-As the polyQ region increases in length, the resulting modification of ataxin-3 secondary structure would be observed as what change in the CD spectrum?

Question

Passage
Spinocerebellar ataxia 3 (SCA3) is a neurodegenerative disease that manifests as a progressive decrease in coordination of limbs and frequently results in impaired speech and eye coordination. It is associated with extension of the polyglutamine (polyQ) region of the ataxin-3 protein. The polyQ region is encoded by a series of consecutive CAG codons known as poly-CAG repeats. These regions vary in length from one person to another, ranging from as few as 10 to as many as 80 repeats. SCA3 has been reported in patients with polyQ regions exceeding ~55 repeats, and increased polyQ length correlates with earlier onset of the disease and greater clinical severity.Circular dichroism (CD) is a method of assessing protein secondary structure. It measures a molecule's ability to absorb left- and right-handed circularly polarized light of varying wavelengths. The absorption difference is known as "ellipticity," denoted by Δε. Alpha-helices have a maximum Δε at 190 nm, and beta-sheets have a maximum Δε at 200 nm.CD results show that as the length of the ataxin-3 polyQ region increases, alpha-helical nature is lost and the protein aggregates, ultimately precipitating out of solution and depositing in brain and other tissues. Furthermore, as proteins aggregate, they form beta-sheets. These beta-sheets are in the parallel orientation, and each sheet can interact with sheets in other proteins to form long, insoluble structures known as amyloid fibers (Figure 1) .

Figure 1 Depiction of the ataxin-3 polyQ region shifting from alpha-helical (cylinders) to beta-sheet (arrows) structure and aggregatingGlutamine can be encoded by both CAG and CAA codons. Researchers investigated survival rates in fruit flies expressing ataxin-3 with polyQ regions of equal length encoded by either CAG-CAG or CAA-CAG repeats (Table 1) . The protein products had identical amino acid sequences.Table 1 Fruit Fly Survival Rates Relative to Ataxin-3 Expression

Adapted from Bevivino AE, Loll PJ. An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils. Proc Natl Acad Sci USA. 2001;98(21) :11955-60.
-As the polyQ region increases in length, the resulting modification of ataxin-3 secondary structure would be observed as what change in the CD spectrum?

Quizplus · Accepted Answer

11ecba2d_0de6_3d36_a3bf_4d81db6c542f_MD0008_00 Circular dichroism (CD) is a classic method of determining a protein's secondary structure based on its "ellipticity" Δε at different wavelengths. According to the passage, alpha-helices have a maximum Δε at 190 nm, and beta sheets have a maximum at 200 nm. The passage also indicates that as the polyQ region of ataxin-3 increases in length, the protein shifts from an alpha to a beta conformation. Therefore, the CD spectra should lose features that correspond to alpha-helices and gain features of beta-sheets as polyQ length increases. In a CD spectrum, this corresponds to the disappearance of the peak at 190 nm and the appearance of a peak at 200 nm. (Choice A) The height of the peak at 190 nm would be expected to decrease as the polyQ length increases, leading to beta-sheet formation. (Choice B) The peak at 190 nm should disappear as the polyQ region increases in length, and the peak at 200 nm should begin to appear. (Choice D) The height of the peak at 200 nm should increase as beta-sheets form when the polyQ region increases in length. Educational objective: Circular dichroism reveals overall protein secondary structure. The spectrum is a combination of structural features: The more alpha-helices a protein has, the more its spectra will look like those of an alpha-helix; the more beta-sheets it has, the more its spectra will look like those of a beta-sheet.

Passage Spinocerebellar Ataxia 3 (SCA3) Is a Neurodegenerative Disease That Manifests