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Integrative structures of the human Cop9 signalosome

Structural dynamics of the human COP9 signalosome revealed by cross-linking mass spectrometry and integrative modeling PubMed logo PDB-Dev

tickVerified to work with the latest stable IMP release (2.17.0). The files are also available at GitHub.
Additional software needed to use these files: IMP numpy MODELLER install instructions

Anaconda logo To install the software needed to reproduce this system with the Anaconda Python command line tool (conda), run the following commands:

conda config --add channels salilab
conda install imp numpy modeller

UCSF logo To set up the environment on the UCSF Wynton cluster to run this system, run:

module load Sali
module load imp python3/numpy modeller
Tags chemical crosslinks MODELLER PMI X-ray

DOI

Integrative Structure Determination of the Human Cop9 Signalosome complex (CSN)

Summary

The COP9 signalosome (CSN) is an evolutionarily conserved eight-subunit (CSN1–8) protein complex that controls protein ubiquitination by deneddylating Cullin-RING E3 ligases (CRLs). The activation and function of CSN hinges on its structural dynamics, which has been challenging to decipher by conventional tools. Here, we determine the interaction and structural dynamics of CSN with the recently discovered ninth subunit, CSN9, in solution. Our results determined the localization of CSN9 binding sites and revealed CSN9-dependent structural changes of CSN. Together with biochemical analysis, we propose a structural model in which CSN9 binding triggers CSN to adopt a configuration that facilitates CSN–CRL interactions, thereby augmenting CSN deneddylase activity. These scripts demonstrate the use of IMP in the modeling of the human Cop9 Signalosome (CSN) complex using multi-crosslinking datasets. The scripts work with the IMP (Release 2.8.0 and newer).

List of files and directories:

Integrative modeling approach summary for this project

Information

Author(s): Ilan E. Chemmama

License: CC BY-SA 4.0 This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International License.

Last known good IMP version: build info build info

Publications: Structural dynamics of the human COP9 signalosome revealed by cross-linking mass spectrometry and integrative modeling.
Craig Gutierrez*, Ilan E. Chemmama*, Haibin Mao, Clinton Yu, Ignacia Echeverria, Sarah A. Block, Scott D. Rychnovsky, Ning Zheng, Andrej Sali, Lan Huang
Proceedings of the National Academy of Sciences Feb 2020, 117 (8) 4088-4098; DOI: 10.1073/pnas.1915542117.
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