Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1.
Proc Natl Acad Sci U S A
; 114(7): 1560-1565, 2017 02 14.
Article
em En
| MEDLINE
| ID: mdl-28143926
ABSTRACT
The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCKBMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCKBMAL1 activity by coactivators and repressors establishes the â¼24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1)CLOCKBMAL1, plays an important role controlling the switch from repression to activation each day. Here we show that CRY1 binds directly to the PAS domain core of CLOCKBMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCKBMAL1 activity by CRY1.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas CLOCK
/
Fatores de Transcrição ARNTL
/
Criptocromos
/
Relógios Circadianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article