Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome

Autor: Nora Cronin, Hugo Yebenes, Edward P. Morris, Anargyros Politis, Kjetil Hansen, Carla Schmidt, Andy M. Lau, Fabienne Beuron, Chloe Martens, Zainab Ahdash, Sarah V. Faull
Přispěvatelé: London Interdisciplinary Biosciences Consortium, Cancer Research UK, Federal Ministry of Education and Research (Germany), European Commission, Lau, Andy M.C., Martens, Chloé, Ahdash, Zainab, Hansen, Kjetil, Schmidt, Carla, Beuron, Fabienne, Morris, Edward P., Politis, Argyris, Lau, Andy M.C. [0000-0003-0572-7826], Martens, Chloé [0000-0002-1617-4238], Ahdash, Zainab [0000-0002-4495-8689], Hansen, Kjetil [0000-0002-0085-8440], Schmidt, Carla [0000-0001-9410-1424], Beuron, Fabienne [0000-0003-1513-6181], Morris, Edward P. [0000-0003-3544-0041], Politis, Argyris [0000-0002-6658-3224]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
General Physics and Astronomy
COP9 Signalosome Complex -- isolation & purification -- metabolism -- ultrastructure
02 engineering and technology
NEDD8
Intracellular Signaling Peptides and Proteins -- isolation & purification -- metabolism
Mass Spectrometry
Ubiquitin-Protein Ligases -- isolation & purification -- metabolism -- ultrastructure
Sf9 Cells
Neddylation
lcsh:Science
chemistry.chemical_classification
Multidisciplinary
biology
Chemistry
Intracellular Signaling Peptides and Proteins
Signal transducing adaptor protein
Sciences bio-médicales et agricoles
021001 nanoscience & nanotechnology
Recombinant Proteins
3. Good health
Cell biology
Ubiquitin ligase
Enzyme mechanisms
Adaptor Proteins
Signal Transducing -- isolation & purification -- metabolism

0210 nano-technology
Cullin
NEDD8 Protein
Science
Ubiquitin-Protein Ligases
macromolecular substances
General Biochemistry
Genetics and Molecular Biology

Article
03 medical and health sciences
Animals
COP9 signalosome
Adaptor Proteins
Signal Transducing

DNA ligase
Peptide Hydrolases -- isolation & purification -- metabolism -- ultrastructure
Mass spectrometry
COP9 Signalosome Complex
Cryoelectron Microscopy
General Chemistry
NEDD8 Protein -- isolation & purification -- metabolism -- ultrastructure
030104 developmental biology
biology.protein
lcsh:Q
Protein Processing
Post-Translational

Recombinant Proteins -- isolation & purification -- metabolism -- ultrastructure
Peptide Hydrolases
Zdroj: Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019)
Nature Communications
Digital.CSIC. Repositorio Institucional del CSIC
instname
Nature communications, 10 (1
Faull, S V, Lau, A, Martens, C P V J, Ahdash, Z M, Hansen, K, Yebenes, H, Schmidt, C, Beuron, F, Cronin, N, Morris, E P & Politis, A 2019, ' Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome ', Nature Communications, vol. 10, no. 1, 3814, pp. 1-13 . https://doi.org/10.1038/s41467-019-11772-y
DOI: 10.1038/s41467-019-11772-y
Popis: 13 p.-5 fig.-1 tab.
Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. © 2019, The Author(s).
The London Interdisciplinary Biosciences Consortium (LIDo) BBSRC Doctoral Training Partnership (BB/M009513/1) supports A.M.C.L. S.V.F., E.P.M. and F.B. are funded by Cancer Research UK (C12209/A16749). C.S. acknowledges funding from the Federal Ministry for Education and Research (BMBF, ZIK programme, 03Z22HN22), the European Regional Development Funds (EFRE, ZS/2016/04/78115) and the MLU Halle-Wittenberg. C.M. and A.P. are funded by the Wellcome Trust (109854/Z/15/Z) and a King’s Health Partners R&D Challenge Fund through the MRC.
Databáze: OpenAIRE