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APCINTERACTIONS SIGNED

Molecular basis for securin and cyclin ubiquitylation by the anaphase-promoting complex (APC/C)

Total Cost €

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EC-Contrib. €

0

Partnership

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Project "APCINTERACTIONS" data sheet

The following table provides information about the project.

Coordinator
UNITED KINGDOM RESEARCH AND INNOVATION 

There are not information about this coordinator. Please contact Fabio for more information, thanks.

 Coordinator Country United Kingdom [UK]
 Project website https://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/david-barford/
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2018-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNITED KINGDOM RESEARCH AND INNOVATION UK (SWINDON) coordinator 183˙454.00
2    MEDICAL RESEARCH COUNCIL UK (SWINDON) coordinator 0.00

Map

 Project objective

This research proposal describes an ambitious effort to characterize structurally and biochemically ubiquitin chain initiation and elongation by the anaphase-promoting complex or cyclosome (APC/C) in complex with two well-characterized substrates. The APC/C is a multi-subunit cullin-RING E3 ubiquitin ligase that controls progression through the cell cycle by a temporal regulation of its activity and substrate specificity. Regulation and specificity of this E3 ligase is achieved through mutually exclusive binding of two structurally related co-activator subunits termed Cdc20 and Cdh1, as well as through APC/C inhibitors, varying substrate affinities and auto-ubiquitylation of its cognate E2s, namely UbcH10 and Ube2S. In order to understand ubiquitin chain initiation and elongation of the two well-known APC/C substrates cyclin B and securin, I am aiming to use a combined approach of cryo-electron microscopy, X-ray crystallography and a variety of biochemical methods. Within this project I will use cryo-electron microscopy studies to uncover the molecular mechanisms of substrate recognition and ubiquitin chain initiation and elongation by analyzing the APC/CCdh1 co-activator complex bound to its transiently associated E2 enzymes Ube2S or UbcH10 and one of the aforementioned high affinity substrates. Crystallization of selected sub-complexes, namely the catalytic core of the APC/C (composed of Apc2 and Apc11) is intended. If obtained, this high-resolution information will then assist the interpretation of the resulting density maps derived from cryo-electron microscopy.

 Publications

year authors and title journal last update
List of publications.
2017 Andreas Boland, Thomas G Martin, Ziguo Zhang, Jing Yang, Xiao-chen Bai, Leifu Chang, Sjors H W Scheres, David Barford
Cryo-EM structure of a metazoan separase–securin complex at near-atomic resolution
published pages: 414-418, ISSN: 1545-9993, DOI: 10.1038/nsmb.3386
Nature Structural & Molecular Biology 24/4 2019-06-13

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