4WSN

Crystal structure of the COP9 signalosome, a P1 crystal form

This is a non-PDB format compatible entry.

Summary for 4WSN

• Entry DOI: 10.2210/pdb4wsn/pdb
• Related: 4d10 4d18
• Descriptor: COP9 signalosome complex subunit 1, COP9 signalosome complex subunit 2, COP9 signalosome complex subunit 3, ... (9 entities in total)
• Functional Keywords: signaling protein, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 48
• Total formula weight: 1935485.77

Authors

Bunker, R.D.,Lingaraju, G.M.,Thoma, N.H. (deposition date: 2014-10-28, release date: 2015-12-23, Last modification date: 2024-01-10)

Primary citation

Cavadini, S.,Fischer, E.S.,Bunker, R.D.,Potenza, A.,Lingaraju, G.M.,Goldie, K.N.,Mohamed, W.I.,Faty, M.,Petzold, G.,Beckwith, R.E.,Tichkule, R.B.,Hassiepen, U.,Abdulrahman, W.,Pantelic, R.S.,Matsumoto, S.,Sugasawa, K.,Stahlberg, H.,Thoma, N.H.
Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome.
Nature, 531:598-603, 2016

PubMed Abstract: The cullin-RING ubiquitin E3 ligase (CRL) family comprises over 200 members in humans. The COP9 signalosome complex (CSN) regulates CRLs by removing their ubiquitin-like activator NEDD8. The CUL4A-RBX1-DDB1-DDB2 complex (CRL4A(DDB2)) monitors the genome for ultraviolet-light-induced DNA damage. CRL4A(DBB2) is inactive in the absence of damaged DNA and requires CSN to regulate the repair process. The structural basis of CSN binding to CRL4A(DDB2) and the principles of CSN activation are poorly understood. Here we present cryo-electron microscopy structures for CSN in complex with neddylated CRL4A ligases to 6.4 Å resolution. The CSN conformers defined by cryo-electron microscopy and a novel apo-CSN crystal structure indicate an induced-fit mechanism that drives CSN activation by neddylated CRLs. We find that CSN and a substrate cannot bind simultaneously to CRL4A, favouring a deneddylated, inactive state for substrate-free CRL4 complexes. These architectural and regulatory principles appear conserved across CRL families, allowing global regulation by CSN.

PubMed: 27029275
DOI: 10.1038/nature17416

Experimental method

X-RAY DIFFRACTION (5.5 Å)