6YEJ

Cryo-EM structure of the Full-length disease type human Huntingtin

Summary for 6YEJ

• Entry DOI: 10.2210/pdb6yej/pdb
• EMDB information: 10793 4937
• Descriptor: Huntingtin (1 entity in total)
• Functional Keywords: multivalent scaffold platform, protein binding, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 355278.72

Authors

Tame, G.,Jung, T.,Dal Perraro, M.,Hebert, H.,Song, J. (deposition date: 2020-03-24, release date: 2020-12-16, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (18.2 Å)