Intramolecular backfolding of the carboxyl-terminal end of MxA protein is a prerequisite for its oligomerization.
J Biol Chem
; 274(45): 32071-8, 1999 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-10542240
ABSTRACT
Mx proteins are large GTPases, which play a pivotal role in the interferon type I-mediated response against viral infections. The human MxA inhibits the replication of several RNA viruses and is organized in oligomeric structures. Using two different experimental approaches, the mammalian two-hybrid system and an interaction dependent nuclear translocation approach, three domains in the carboxyl-terminal moiety were identified that are involved in the oligomerization of MxA. The first consists of a carboxyl-terminal amphipathic helix (LZ1), which binds to a more proximal part of the same molecule. This intramolecular backfolding is a prerequisite for the formation of an intermolecular complex. This intermolecular interaction is mediated by two domains, a poorly defined region generated by the intramolecular interaction and a domain located between amino acids 363 and 415. Co-expression of wild-type MxA with various mutant fragments thereof revealed that the presence of the carboxyl-terminal region comprising the amphipathic helices LZ1 and LZ2 is necessary and sufficient to exert a dominant negative effect. This finding suggests that the functional interference of the carboxyl-terminal region is due to competition for binding of an as yet unidentified cellular or viral target molecules.
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Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Pliegue de Proteína
/
Proteínas de Unión al GTP
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
1999
Tipo del documento:
Article
País de afiliación:
Suiza