A conserved tryptophan at the membrane-water interface acts as a gatekeeper for Kir6.2/SUR1 channels and causes neonatal diabetes when mutated.
J Physiol
; 589(Pt 13): 3071-83, 2011 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-21540348
ABSTRACT
We identified a novel heterozygous mutation, W68R, in the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel, in a patient with transient neonatal diabetes. This tryptophan is absolutely conserved in mammalian Kir channels. The functional effects of mutations at residue 68 of Kir6.2 were studied by heterologous expression in Xenopus oocytes, and by homology modelling. We found the Kir6.2-W68R mutation causes a small reduction in ATP inhibition in the heterozygous state and an increase in the whole-cell KATP current. This can explain the clinical phenotype of the patient. The effect of the mutation was not charge or size dependent, the order of potency for ATP inhibition being W
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Droga
/
Triptofano
/
Membrana Celular
/
Transportadores de Cassetes de Ligação de ATP
/
Canais de Potássio Corretores do Fluxo de Internalização
/
Diabetes Mellitus
/
Doenças do Recém-Nascido
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Child
/
Female
/
Humans
/
Newborn
Idioma:
En
Revista:
J Physiol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido