B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of α-dystroglycan.
Elife
; 32014 Oct 03.
Article
en En
| MEDLINE
| ID: mdl-25279697
ABSTRACT
Recent studies demonstrated that mutations in B3GNT1, an enzyme proposed to be involved in poly-N-acetyllactosamine synthesis, were causal for congenital muscular dystrophy with hypoglycosylation of α-dystroglycan (secondary dystroglycanopathies). Since defects in the O-mannosylation protein glycosylation pathway are primarily responsible for dystroglycanopathies and with no established O-mannose initiated structures containing a ß3 linked GlcNAc known, we biochemically interrogated this human enzyme. Here we report this enzyme is not a ß-1,3-N-acetylglucosaminyltransferase with catalytic activity towards ß-galactose but rather a ß-1,4-glucuronyltransferase, designated B4GAT1, towards both α- and ß-anomers of xylose. The dual-activity LARGE enzyme is capable of extending products of B4GAT1 and we provide experimental evidence that B4GAT1 is the priming enzyme for LARGE. Our results further define the functional O-mannosylated glycan structure and indicate that B4GAT1 is involved in the initiation of the LARGE-dependent repeating disaccharide that is necessary for extracellular matrix protein binding to O-mannosylated α-dystroglycan that is lacking in secondary dystroglycanopathies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
N-Acetilglucosaminiltransferasas
/
Distroglicanos
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos