Regulation of Torsin ATPases by LAP1 and LULL1.
Proc Natl Acad Sci U S A
; 110(17): E1545-54, 2013 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-23569223
ABSTRACT
TorsinA is a membrane-associated AAA+ (ATPases associated with a variety of cellular activities) ATPase implicated in primary dystonia, an autosomal-dominant movement disorder. We reconstituted TorsinA and its cofactors in vitro and show that TorsinA does not display ATPase activity in isolation; ATP hydrolysis is induced upon association with LAP1 and LULL1, type II transmembrane proteins residing in the nuclear envelope and endoplasmic reticulum. This interaction requires TorsinA to be in the ATP-bound state, and can be attributed to the luminal domains of LAP1 and LULL1. This ATPase activator function controls the activities of other members of the Torsin family in distinct fashion, leading to an acceleration of the hydrolysis step by up to two orders of magnitude. The dystonia-causing mutant of TorsinA is defective in this activation mechanism, suggesting a loss-of-function mechanism for this congenital disorder.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
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Adenosina Trifosfatases
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Chaperonas Moleculares
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Distonia Muscular Deformante
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Retículo Endoplasmático
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Proteínas de Choque Térmico HSC70
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos