7DXJ

Human 46QHuntingtin-HAP40 complex structure

Summary for 7DXJ

• Entry DOI: 10.2210/pdb7dxj/pdb
• EMDB information: 30911
• Descriptor: Huntingtin, 40-kDa huntingtin-associated protein (2 entities in total)
• Functional Keywords: huntingtin, 46q, hap40, structural protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 390333.19

Authors

Guo, Q.,Fernandez-Busnadiego, R. (deposition date: 2021-01-19, release date: 2021-03-24, Last modification date: 2021-10-06)

Primary citation

Huang, B.,Guo, Q.,Niedermeier, M.L.,Cheng, J.,Engler, T.,Maurer, M.,Pautsch, A.,Baumeister, W.,Stengel, F.,Kochanek, S.,Fernandez-Busnadiego, R.
Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex.
Structure, 29:804-809.e5, 2021

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 (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.

PubMed: 33909994
DOI: 10.1016/j.str.2021.04.003

Experimental method

ELECTRON MICROSCOPY (3.6 Å)