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-Structure paper
Title | Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates. |
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Journal, issue, pages | Commun Biol, Vol. 4, Issue 1, Page 849, Year 2021 |
Publish date | Jul 8, 2021 |
Authors | Jesús G Galaz-Montoya / Sarah H Shahmoradian / Koning Shen / Judith Frydman / Wah Chiu / |
PubMed Abstract | Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder caused by an expanded poly-glutamine (polyQ) tract in the mutant huntingtin (mHTT) protein. The formation and topology of ...Huntington disease (HD) is a neurodegenerative trinucleotide repeat disorder caused by an expanded poly-glutamine (polyQ) tract in the mutant huntingtin (mHTT) protein. The formation and topology of filamentous mHTT inclusions in the brain (hallmarks of HD implicated in neurotoxicity) remain elusive. Using cryo-electron tomography and subtomogram averaging, here we show that mHTT exon 1 and polyQ-only aggregates in vitro are structurally heterogenous and filamentous, similar to prior observations with other methods. Yet, we find filaments in both types of aggregates under ~2 nm in width, thinner than previously reported, and regions forming large sheets. In addition, our data show a prevalent subpopulation of filaments exhibiting a lumpy slab morphology in both aggregates, supportive of the polyQ core model. This provides a basis for future cryoET studies of various aggregated mHTT and polyQ constructs to improve their structure-based modeling as well as their identification in cells without fusion tags. |
External links | Commun Biol / PubMed:34239038 / PubMed Central |
Methods | EM (subtomogram averaging) |
Resolution | 32.0 - 35.0 Å |
Structure data | EMDB-21248: EMDB-21253: |
Source |
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