Structural dynamics of the human COP9 signalosome revealed by cross-linking mass spectrometry and integrative modeling.

ABSTRACT: 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 have developed a multichemistry cross-linking mass spectrometry approach enabled by three mass spectometry-cleavable cross-linkers to generate highly reliable cross-link data. We applied this approach with integrative structure modeling to 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.

SUBMITTER: Gutierrez C 

PROVIDER: S-EPMC7049115 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature