AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270).
J Biol Chem
; 280(14): 13395-400, 2005 Apr 08.
Article
em En
| MEDLINE
| ID: mdl-15695819
ABSTRACT
AMP-activated protein kinase (AMPK) is an important metabolic stress-sensing protein kinase responsible for regulating metabolism in response to changing energy demand and nutrient supply. Mammalian AMPK is a stable alphabetagamma heterotrimer comprising a catalytic alpha and two non-catalytic subunits, beta and gamma. The beta subunit targets AMPK to membranes via an N-terminal myristoyl group and to glycogen via a mid-molecule glycogen-binding domain. Here we find that the conserved C-terminal 85-residue sequence of the beta subunit, beta1-(186-270), is sufficient to form an active AMP-dependent heterotrimer alpha1beta1-(186-270)-gamma1, whereas the 25-residue beta1 C-terminal (246-270) sequence is sufficient to bind gamma1, gamma2, or gamma3 but not the alpha subunit. Deletion of the beta C-terminal Ile-270 precludes betagamma association in the absence of the alpha subunit, but the presence of the alpha subunit or substitution of Ile-270 with Ala or Glu restores betagamma binding. Truncation of the alpha subunit reveals that beta1 binding requires the alpha1-(313-473) sequence. The conserved C-terminal 85-residue sequence of the beta subunit (90% between beta1 and beta2) is the primary alphagamma binding sequence responsible for the formation of the AMPK alphabetagamma heterotrimer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Estrutura Quaternária de Proteína
/
Subunidades Proteicas
/
Complexos Multienzimáticos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article