| RRC ID |
61363
|
| 著者 |
Toma-Fukai S, Hibi R, Naganuma T, Sakai M, Saijo S, Shimizu N, Matsumoto M, Shimizu T.
|
| タイトル |
Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure.
|
| ジャーナル |
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.
|
| 巻・号 |
295(43)
|
| ページ |
14630-14639
|
| 公開日 |
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
|
| リソース情報 |
| 遺伝子材料 |
Genome Network Project Human cDNA Clone
IRAK072A12 (HGY028812)
IRAK133C02 (HGY053250) |
