High affinity binding between Hsp70 and the C-terminal domain of the measles virus nucleoprotein requires an Hsp40 co-chaperone.
J Mol Recognit
; 23(3): 301-15, 2010.
Article
em En
| MEDLINE
| ID: mdl-19718689
ABSTRACT
The major inducible 70 kDa heat shock protein (hsp70) binds the measles virus (MeV) nucleocapsid with high affinity in an ATP-dependent manner, stimulating viral transcription and genome replication, and profoundly influencing virulence in mouse models of brain infection. Binding is mediated by two hydrophobic motifs (Box-2 and Box-3) located within the C-terminal domain (N(TAIL)) of the nucleocapsid protein, with N(TAIL) being an intrinsically disordered domain. The current work showed that high affinity hsp70 binding to N(TAIL) requires an hsp40 co-chaperone that interacts primarily with the hsp70 nucleotide binding domain (NBD) and displays no significant affinity for N(TAIL). Hsp40 directly enhanced hsp70 ATPase activity in an N(TAIL)-dependent manner, and formation of hsp40-hsp70-N(TAIL) intracellular complexes required the presence of N(TAIL) Box-2 and 3. Results are consistent with the functional interplay between hsp70 nucleotide and substrate binding domains (SBD), where ATP hydrolysis is rate limiting to high affinity binding to client proteins and is enhanced by hsp40. As such, hsp40 is an essential variable in understanding the outcome of MeV-hsp70 interactions.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Virais
/
Proteínas de Choque Térmico HSP70
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Proteínas de Choque Térmico HSP40
/
Nucleoproteínas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Mol Recognit
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França