RRC ID 61363
Author Toma-Fukai S, Hibi R, Naganuma T, Sakai M, Saijo S, Shimizu N, Matsumoto M, Shimizu T.
Title Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure.
Journal J Biol Chem
Abstract 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 Å 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.
Volume 295(43)
Pages 14630-14639
Published 2020-10-23
DOI 10.1074/jbc.RA120.013431
PII S0021-9258(17)49341-0
PMID 32820047
PMC PMC7586209
MeSH Animals Crystallography, X-Ray Humans Mice Models, Molecular Protein Conformation Protein Domains Ubiquitin-Protein Ligases / chemistry* Ubiquitin-Protein Ligases / metabolism Ubiquitination p300-CBP Transcription Factors / chemistry* p300-CBP Transcription Factors / metabolism
IF 4.238
DNA material Genome Network Project Human cDNA Clone IRAK072A12 (HGY028812) IRAK133C02 (HGY053250)