+Search query
-Structure paper
Title | Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex. |
---|---|
Journal, issue, pages | Structure, Vol. 29, Issue 8, Page 804-809.e5, Year 2021 |
Publish date | Aug 5, 2021 |
Authors | Bin Huang / Qiang Guo / Marie L Niedermeier / Jingdong Cheng / Tatjana Engler / Melanie Maurer / Alexander Pautsch / Wolfgang Baumeister / Florian Stengel / Stefan Kochanek / Rubén Fernández-Busnadiego / |
PubMed Abstract | The abnormal 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 polyglutamine ...The abnormal 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 polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40). Surprisingly, our comprehensive biophysical, crosslinking mass spectrometry and cryo-EM experiments revealed no major differences in the conformation of HTT-HAP40 complexes of various polyQ length, including 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients), and 128QHTT-HAP40 (extreme polyQ length). Thus, HTT polyQ expansion does not alter the global conformation of HTT when associated with HAP40. |
External links | Structure / PubMed:33909994 |
Methods | EM (single particle) |
Resolution | 3.6 - 4.1 Å |
Structure data | EMDB-30911, PDB-7dxj: EMDB-30912, PDB-7dxk: |
Source |
|
Keywords | STRUCTURAL PROTEIN / Huntingtin / 46Q / HAP40 / 128Q |