6RMH

The Rigid-body refined model of the normal Huntingtin.

6RMH の概要

• エントリーDOI: 10.2210/pdb6rmh/pdb
• EMDBエントリー: 4937
• 分子名称: Huntingtin (1 entity in total)
• 機能のキーワード: multivalent scaffold platform, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 347974.91

構造登録者

Jung, T.,Tamo, G.,Dal Perraro, M.,Hebert, H.,Song, J. (登録日: 2019-05-06, 公開日: 2020-06-03, 最終更新日: 2024-11-13)

主引用文献

Jung, T.,Shin, B.,Tamo, G.,Kim, H.,Vijayvargia, R.,Leitner, A.,Marcaida, M.J.,Astorga-Wells, J.,Jung, R.,Aebersold, R.,Peraro, M.D.,Hebert, H.,Seong, I.S.,Song, J.J.
The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain.
Structure, 28:1035-1050.e8, 2020

PubMed Abstract: The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural information on its HEAT-repeat domains. Here, we present analyses of the impact of polyQ length on the structure and function of HTT via an integrative structural and biochemical approach. The cryo-EM analysis of normal (Q23) and disease (Q78) type HTTs shows that the structures of apo HTTs significantly differ from the structure of HTT in a HAP40 complex and that the polyQ expansion induces global structural changes in the relative movements among the HTT domains. In addition, we show that the polyQ expansion alters the phosphorylation pattern across HTT and that Ser2116 phosphorylation in turn affects the global structure and function of HTT. These results provide a molecular basis for the effect of the polyQ segment on HTT structure and activity, which may be important for HTT pathology.

PubMed: 32668197
DOI: 10.1016/j.str.2020.06.008

実験手法

ELECTRON MICROSCOPY (9.6 Å)