Model for the interaction of gammaherpesvirus 68 RING-CH finger protein mK3 with major histocompatibility complex class I and the peptide-loading complex.
J Virol
; 78(16): 8673-86, 2004 Aug.
Article
em En
| MEDLINE
| ID: mdl-15280476
ABSTRACT
The mK3 protein of gammaherpesvirus 68 and the kK5 protein of Kaposi's sarcoma-associated herpesvirus are members of a family of structurally related viral immune evasion molecules that all possess a RING-CH domain with ubiquitin ligase activity. These proteins modulate the expression of major histocompatibility complex class I molecules (mK3 and kK5) as well as other molecules like ICAM-1 and B7.2 (kK5). Previously, mK3 was shown to ubiquitinate nascent class I molecules, resulting in their rapid degradation, and this process was found to be dependent on TAP and tapasin, endoplasmic reticulum molecules involved in class I assembly. Here, we demonstrate that in murine cells, kK5 does not affect class I expression but does downregulate human B7.2 molecules in a TAP/tapasin-independent manner. These differences in substrate specificity and TAP/tapasin dependence between mK3 and kK5 permitted us, using chimeric molecules, to map the sites of mK3 interaction with TAP/tapasin and to determine the requirements for substrate recognition by mK3. Our findings indicate that mK3 interacts with TAP1 and -2 via their C-terminal domains and with class I molecules via their N-terminal domains. Furthermore, by orienting the RING-CH domain of mK3 appropriately with respect to class I, mK3 binding to TAP/tapasin, rather than the presence of unique sequences in class I, appears to be the primary determinant of substrate specificity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Imunoglobulinas
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Antígenos de Histocompatibilidade Classe I
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Gammaherpesvirinae
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Antiporters
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Transportadores de Cassetes de Ligação de ATP
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Ubiquitina-Proteína Ligases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article