English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The cryo-electron microscopy structure of huntingtin

Kochanek, S., Huang, B., Seefelder, M., Engler, T., Cheng, J., Baumeister, W., et al. (2018). The cryo-electron microscopy structure of huntingtin. Journal of Neurology, Neurosurgery and Psychiatry, 89(Suppl 1), A5-A5.

Item is

Basic

show hide
Genre: Meeting Abstract
Other : Meeting Abstract: A12

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Kochanek, Stefan1, Author
Huang, Bin1, Author
Seefelder, Manuel1, Author
Engler, Tatjana1, Author
Cheng, Jingdong1, Author
Baumeister, Wolfgang2, Author              
Guo, Qiang2, Author              
Fernandez-Busnadiego, Ruben2, Author              
Affiliations:
1external, ou_persistent22              
2Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565142              

Content

show
hide
Free keywords: Neurosciences & Neurology; Psychiatry; Surgery;
 Abstract: Huntingtin (HTT) is the protein that is altered in Huntington’s disease (HD). While HTT has been found to be essential for many cellular activities including transport of vesicles in the cell, cellular uptake of materials (endocytosis), cellular degradation of waste (autophagy), regulation of transcription, and even is important for embryonic development, an integrating understanding of HTT’s many biological functions at the molecular level is still missing. Although the HTT gene and the disease-causing mutation have been identified 25 years ago, very little data has been available on the structure of HTT. However, information on HTT’s structure would be very important for achieving an improved understand of HTT’s function in health and disease. Here we employed cryo-electron microscopy (cryo-EM) to determine the structure of full-length human HTT in a complex with another protein, HTT-associated protein 40 (HAP40). This interaction of HTT with HAP40 was instrumental in stabilizing HTT’s structure to a degree that the structure of HTT could be determined at detailed level at an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The N- and C-terminal domains contain multiple HEAT repeat elements that are arranged in a solenoid fashion. These domains are connected by a smaller bridge domain that contain different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat (TPR)-like organization. HAP40 binds in a cleft contacting the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing HTT’s conformation. These data help in the interpretation of previous biochemical results and will pave the way for the generation and testing of new research hypotheses that ultimately will lead to an improved understanding of HTT’s diverse biological functions.

Details

show
hide
Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 1
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000446126000013
DOI: 10.1136/jnnp-2018-EHDN.12
 Degree: -

Event

show
hide
Title: Plenary Meeting of the European-Huntington's-Disease-Network (EHDN)
Place of Event: Vienna, AUSTRIA
Start-/End Date: 2018 - 2018

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Neurology, Neurosurgery and Psychiatry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: BMJ PUBLISHING GROUP
Pages: - Volume / Issue: 89 (Suppl 1) Sequence Number: - Start / End Page: A5 - A5 Identifier: ISSN: 0022-3050