Structural insights into SETD3-mediated histidine methylation on ß-actin.
Elife
; 82019 02 20.
Article
en En
| MEDLINE
| ID: mdl-30785395
ABSTRACT
SETD3 is a member of the SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Previously, we identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on ß-actin (Kwiatkowski et al., 2018). Here, we present two structures of S-adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified ß-actin peptide or its His-methylated variant. Structural analyses, supported by biochemical experiments and enzyme activity assays, indicate that the recognition and methylation of ß-actin by SETD3 are highly sequence specific, and that both SETD3 and ß-actin adopt pronounced conformational changes upon binding to each other. In conclusion, this study is the first to show a catalytic mechanism of SETD3-mediated histidine methylation on ß-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors of SETD3.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Conformación Proteica
/
S-Adenosilhomocisteína
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Actinas
/
Histona Metiltransferasas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Elife
Año:
2019
Tipo del documento:
Article
País de afiliación:
China