4.6 Article

Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 43, Pages 14630-14639

Publisher

ELSEVIER
DOI: 10.1074/jbc.RA120.013431

Keywords

GCN5; E3 ligase; ubiquitination; Zn ion; crystal structure; E3 ubiquitin ligase; ubiquitin ligase; structural biology; zinc finger; GCN5

Funding

  1. Japanese Ministry of Education, Culture, Sports, Science, and Technology
  2. CREST JST

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General control nonderepressible 5 (GCN5, also known as Kat2a) and p300/CBP-associated factor (PCAF, also known as Kat2b) are two homologous acetyltransferases. Both proteins share similar domain architecture consisting of a PCAF N-terminal (PCAF_N) domain, acetyltransferase domain, and a bromodomain. PCAF also acts as a ubiquitin E3 ligase whose activity is attributable to the PCAF_N domain, but its structural aspects are largely unknown. Here, we demonstrated that GCN5 exhibited ubiquitination activity in a similar manner to PCAF and its activity was supported by the ubiquitin-conjugating enzyme UbcH5. Moreover, we determined the crystal structure of the PCAF_N domain at 1.8 angstrom resolution and found that PCAF_N domain folds into a helical structure with a characteristic binuclear zinc region, which was not predicted from sequence analyses. The zinc region is distinct from known E3 ligase structures, suggesting this region may form a new class of E3 ligase. Our biochemical and structural study provides new insight into not only the functional significance of GCN5 but also into ubiquitin biology.

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