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• W2802935265 startingPage "1847" @default.
• W2802935265 abstract "Polyglutamine (polyQ) diseases, including Huntington's disease, result from the aggregation of an abnormally expanded polyQ repeat in the affected protein. The length of the polyQ repeat is essential for the disease's onset; however, the molecular mechanism of polyQ aggregation is still poorly understood. Controlled conditions and initiation of the aggregation process are prerequisites for the detection of transient intermediate states. We present an attenuated total reflection Fourier-transform infrared spectroscopic approach combined with protein immobilization to study polyQ aggregation dependent on the polyQ length. PolyQ proteins were engineered mimicking the mammalian N-terminus fragment of the Huntingtin protein and containing a polyQ sequence with the number of glutamines below (Q11), close to (Q38), and above (Q56) the disease threshold. A monolayer of the polyQ construct was chemically immobilized on the internal reflection element of the attenuated total reflection cell, and the aggregation was initiated via enzymatic cleavage. Structural changes of the polyQ sequence were monitored by time-resolved infrared difference spectroscopy. We observed faster aggregation kinetics for the longer sequences, and furthermore, we could distinguish β-structured intermediates for the different constructs, allowing us to propose aggregation mechanisms dependent on the repeat length. Q11 forms a β-structured aggregate by intermolecular interaction of stretched monomers, whereas Q38 and Q56 undergo conformational changes to various β-structured intermediates, including intramolecular β-sheets." @default.
• W2802935265 created "2018-05-17" @default.
• W2802935265 creator A5031225581 @default.
• W2802935265 creator A5056734233 @default.
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• W2802935265 date "2018-04-01" @default.
• W2802935265 modified "2023-10-14" @default.
• W2802935265 title "Insights into the Aggregation Mechanism of PolyQ Proteins with Different Glutamine Repeat Lengths" @default.
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• W2802935265 doi "https://doi.org/10.1016/j.bpj.2018.02.037" @default.
• W2802935265 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5937114" @default.
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• W2802935265 hasPublicationYear "2018" @default.
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