English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Electron microscopy structure of human APC/C-CDH1-EMI1 reveals multimodal mechanism of E3 ligase shutdown.

Frye, J., Brown, N. G., Petzold, G., Watson, E. R., Grace, C. R. R., Nourse, A., et al. (2013). Electron microscopy structure of human APC/C-CDH1-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nature Structural and Molecular Biology, 20(7), 827-835. doi:10.1038/nsmb.2593.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-1732-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-1DE8-0
Genre: Journal Article

Files

show Files
hide Files
:
1819434.pdf (Publisher version), 3MB
Name:
1819434.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1819434_Supplement_1.pdf (Supplementary material), 8MB
Name:
1819434_Supplement_1.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Frye, J., Author
Brown, N. G., Author
Petzold, G., Author
Watson, E. R., Author
Grace, C. R. R., Author
Nourse, A., Author
Jarvis, M. A., Author
Kriwacki, R. W., Author
Peters, J. M., Author
Stark, H.1, Author              
Schulman, B. A., Author
Affiliations:
1Research Group of 3D Electron Cryo-Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578577              

Content

show
hide
Free keywords: -
 Abstract: The anaphase-promoting complex/cyclosome (APC/C) is a similar to 1.5-MDa multiprotein E3 ligase enzyme that regulates cell division by promoting timely ubiquitin-mediated proteolysis of key cell-cycle regulatory proteins. Inhibition of human APC/C-CDH1 during interphase by early mitotic inhibitor 1 (EMI1) is essential for accurate coordination of DNA synthesis and mitosis. Here, we report a hybrid structural approach involving NMR, electron microscopy and enzymology, which reveal that EMI1's 143-residue C-terminal domain inhibits multiple APC/C-CDH1 functions. The intrinsically disordered D-box, linker and tail elements, together with a structured zinc-binding domain, bind distinct regions of APC/C-CDH1 to synergistically both block the substrate-binding site and inhibit ubiquitin-chain elongation. The functional importance of intrinsic structural disorder is explained by enabling a small inhibitory domain to bind multiple sites to shut down various functions of a 'molecular machine' nearly 100 times its size.

Details

show
hide
Language(s): eng - English
 Dates: 2013-05-262013-07
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/nsmb.2593
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature Structural and Molecular Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 20 (7) Sequence Number: - Start / End Page: 827 - 835 Identifier: -