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PolyQ-expansion does not alter the huntingtin-HAP40 complex

ABSTRACT: The amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington’s disease (HD). At the protein level, this translates into the expansion of a poly-glutamine (polyQ) stretch in the HTT N-terminus, which renders HTT aggregation-prone by unknown mechanisms. Here we investigate the effects of polyQ expansion on the HTT-HAP40 complex, where HTT structure is substantially stabilized. Surprisingly, our biophysical, cryo-EM and crosslinking mass spectrometry experiments reveal no major changes between 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients) and 128QHTT-HAP40 (extreme polyQ length). Thus, the proposed destabilizing effect of HTT polyQ expansion may not suffice to alter the HTT-HAP40 complex, suggesting that polyQ expansion does not have a major global effect on HTT structure.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Huntington Disease

SUBMITTER: Florian Stengel

LAB HEAD: Florian Stengel

PROVIDER: PXD018451 | Pride | 2021-03-19

REPOSITORIES: Pride

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			Action	DRS
	10_HttQ128_I_result_targHits_ld25.xls	Xls
	11_HttQ128_II_result_targHits_ld25.xls	Xls
	12_HttQ128_III_result_targHits_ld25.xls	Xls
	4_HttQ17_I_result_targetHits_ld25.xls	Xls
	5_HttQ17_II_result_targetHits_ld25.xls	Xls

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