Related Experiment Video
Updated: Jun 1, 2026

Monitoring Protein Aggregation Kinetics In Vivo using Automated Inclusion Counting in Caenorhabditis elegans
Published on: December 17, 2021
Location trumps length: polyglutamine-mediated changes in folding and aggregation of a host protein
Matthew D Tobelmann1, Regina M Murphy
1Department of Chemical and Biological Engineering, University of Wisconsin, Madison, Wisconsin, USA.
Abstract:
Expanded CAG diseases are progressive neurodegenerative disorders in which specific proteins have an unusually long polyglutamine stretch. Although these proteins share no other sequence or structural homologies, they all aggregate into intracellular inclusions that are believed to be pathological. We sought to determine what impact the position and number of glutamines have on the structure and aggregation of the host protein, apomyoglobin. Variable-length polyQ tracts were inserted either into the loop between the C- and D-helices (Q(n)CD) or at the N-terminus (Q(n)NT). The Q(n)CD mutants lost some α-helix and gained unordered and/or β-sheet in a length-dependent manner. These mutants were partially unfolded and rapidly assembled into soluble chain-like oligomers. In sharp contrast, the Q(n)NT mutants largely retained wild-type tertiary structure but associated into long, fibrillar aggregates. Control proteins with glycine-serine repeats (GS(8)CD and GS(8)NT) were produced. GS(8)CD exhibited similar structural perturbations and aggregation characteristics to an analogously sized Q(16)CD, indicating that the observed effects are independent of amino acid composition. In contrast to Q(16)NT, GS(8)NT did not form fibrillar aggregates. Thus, soluble oligomers are produced through structural perturbation and do not require polyQ, whereas classic fibrils arise from specific polyQ intermolecular interactions in the absence of misfolding.
Related Concept Videos
Protein Folding
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Folding
Protein Organization
Protein Organization
The primary structure of a protein is its amino acid sequence.
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Molecular Chaperones and Protein Folding
The...

