Structures of the Phactr1 RPEL domain and RPEL motif complexes with G-actin reveal the molecular basis for actin binding cooperativity.
Structure
; 20(11): 1960-70, 2012 Nov 07.
Article
en En
| MEDLINE
| ID: mdl-23041370
ABSTRACT
The Phactr family of PP1-binding proteins and the myocardin-related transcription factor family of transcriptional coactivators contain regulatory domains comprising three copies of the RPEL motif, a G-actin binding element. We report the structure of a Phactr1 G-actinâ
RPEL domain complex. Three G-actins surround the crank-shaped RPEL domain forming a closed helical assembly. Their spatial relationship is identical to the RPEL-actins within the pentavalent MRTF G-actinâ
RPEL domain complex, suggesting that conserved cooperative interactions between actinâ
RPEL units organize the assembly. In the trivalent Phactr1 complex, each G-actinâ
RPEL unit makes secondary contacts with its downstream actin involving distinct RPEL residues. Similar secondary contacts are seen in G-actinâ
RPEL peptide crystals. Loss-of-secondary-contact mutations destabilize the Phactr1 G-actinâ
RPEL assembly. Furthermore, actin-mediated inhibition of Phactr1 nuclear import requires secondary contact residues in the Phactr1 N-terminal RPEL-N motif, suggesting that it involves interaction of RPEL-N with the C-terminal assembly. Secondary actin contacts by actin-bound RPEL motifs thus govern formation of multivalent actinâ
RPEL assemblies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Actinas
/
Proteínas de Microfilamentos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido