Crystal structure of the PH-BEACH domains of human LRBA/BGL.
Biochemistry
; 43(47): 14873-80, 2004 Nov 30.
Article
en En
| MEDLINE
| ID: mdl-15554694
The beige and Chediak-Higashi syndrome (BEACH) domain defines a large family of eukaryotic proteins that have diverse cellular functions in vesicle trafficking, membrane dynamics, and receptor signaling. The domain is the only module that is highly conserved among all of these proteins, but the exact functions of this domain and the molecular basis for its actions are currently unknown. Our previous studies showed that the BEACH domain is preceded by a novel, weakly conserved pleckstrin homology (PH) domain. We report here the crystal structure at 2.4 A resolution of the PH-BEACH domain of human LRBA/BGL. The PH domain has the same backbone fold as canonical PH domains, despite sharing no sequence homology with them. However, our binding assays demonstrate that the PH domain in the BEACH proteins cannot bind phospholipids. The BEACH domain contains a core of several partially extended peptide segments that is flanked by helices on both sides. The structure suggests intimate association between the PH and the BEACH domains, and surface plasmon resonance studies confirm that the two domains of the protein FAN have high affinity for each other, with a K(d) of 120 nM.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estructura Terciaria de Proteína
/
Proteínas Quinasas Dependientes de AMP Cíclico
/
Cristalografía por Rayos X
/
Proteínas del Tejido Nervioso
Idioma:
En
Revista:
Biochemistry
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos