Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure
| Autor: | Toshiyuki Shimizu, Takao Naganuma, Sachiko Toma-Fukai, Shinya Saijo, Nobutaka Shimizu, Mashito Sakai, Ryota Hibi, Michihiro Matsumoto |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular 0301 basic medicine Architecture domain Protein Conformation Ubiquitin-Protein Ligases Crystallography X-Ray Biochemistry Mice 03 medical and health sciences Protein Domains Ubiquitin Animals Humans p300-CBP Transcription Factors Molecular Biology Zinc finger 030102 biochemistry & molecular biology biology Ubiquitination Cell Biology Ubiquitin ligase Bromodomain Cell biology 030104 developmental biology Structural biology PCAF Acetyltransferase Protein Structure and Folding biology.protein |
| Zdroj: | J Biol Chem |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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