Crystal structure of GCN5 PCAF N-terminal domain reveals atypical ubiquitin ligase structure.
E3 ligase
E3 ubiquitin ligase
GCN5
Zn ion
crystal structure
structural biology
ubiquitin ligase
ubiquitination
zinc finger
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
23 10 2020
23 10 2020
Historique:
received:
12
03
2020
revised:
22
07
2020
pubmed:
21
8
2020
medline:
10
3
2021
entrez:
22
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32820047
pii: S0021-9258(17)49341-0
doi: 10.1074/jbc.RA120.013431
pmc: PMC7586209
pii:
doi:
Substances chimiques
p300-CBP Transcription Factors
EC 2.3.1.48
p300-CBP-associated factor
EC 2.3.1.48
Ubiquitin-Protein Ligases
EC 2.3.2.27
Banques de données
PDB
['2y0n', '7BY1']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14630-14639Informations de copyright
© 2020 Toma-Fukai et al.
Déclaration de conflit d'intérêts
Conflict of interest—All authors declare no conflict of interest in this work.
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