Cullin; CSN; Structural biology; DNA repair; E3 Ubiquitin ligases; Ubiquitination; COP9 signalosome
Lingaraju Gondichatnahalli M., Lingaraju Gondichatnahalli M., Bunker Richard D., Bunker Richard D., Cavadini Simone, Cavadini Simone, Hess Daniel, Hassiepen Ulrich, Renatus Martin, Fischer Eric S., Fischer Eric S., Thomä Nicolas H., Thomä Nicolas H. (2014), Crystal structure of the human COP9 signalosome, in Nature
, 512(7513), 161-165.
We aim to focus on the molecular mechanism of COP9 signalosome function, examining ways by which it regulates cullin type E3 ubiquitin ligases. The COP9 signalosome (CSN) is composed of 8-subunits, and has structural resemblance to eIF3 and the 26S proteasome lid. CSN functions as an isopeptidase through its CSN5 subunit, with which it removes the ubiquitin-like NEDD8 modifier from the cullin arm. NEDD8 is considered an activator; its removal renders the ligase complex inactive. The signalosome serves as master repressor of cullin type E3 ligases (incl. CUL1, CUL2, CUL3, CUL4, CUL5 and CUL7 families). We will pursue a structural approach examining how the signalosome serves to regulate and inhibit different, structurally diverse, families of cullin ligases.