The intertransmembrane region of Kaposi's sarcoma-associated herpesvirus modulator of immune recognition 2 contributes to B7-2 downregulation
| Autor: | Mizuho Kajikawa, Satoshi Ishido, Mika Ikegaya, Pai-Chi Li, Masami Aoki-Kawasumi, Yuji Sugita, Naoyuki Miyashita, Mari Mito-Yoshida, Eiji Goto |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Immunology Down-Regulation Biology Endocytosis Major histocompatibility complex medicine.disease_cause Microbiology Virus Protein Structure Secondary Cell Line Viral Proteins Immune system Ubiquitin Downregulation and upregulation Virology MHC class I medicine Humans Kaposi's sarcoma-associated herpesvirus Amino Acids Molecular biology Protein Structure Tertiary Virus-Cell Interactions Insect Science Herpesvirus 8 Human biology.protein Mutagenesis Site-Directed B7-2 Antigen |
| Zdroj: | Journal of virology. 86(9) |
| ISSN: | 1098-5514 |
| Popis: | Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor virus, encodes two homologous membrane-associated E3 ubiquitin ligases, modulator of immune recognition 1 (MIR1) and MIR2, to evade host immunity. Both MIR1 and MIR2 downregulate the surface expression of major histocompatibility complex class I (MHC I) molecules through ubiquitin-mediated endocytosis followed by lysosomal degradation. Since MIR2 additionally downregulates a costimulatory molecule (B7-2) and an integrin ligand (intercellular adhesion molecule 1 [ICAM-1]), MIR2 is thought to be a more important molecule for immune evasion than MIR1; however, the molecular basis of the MIR2 substrate specificity remains unclear. To address this issue, we determined which regions of B7-2 and MIR2 are required for MIR2-mediated B7-2 downregulation. Experiments with chimeras made by swapping domains between human B7-2 and CD8α, a non-MIR2 substrate, and between MIR1 and MIR2 demonstrated a significant contribution of the juxtamembrane (JM) region of B7-2 and the intertransmembrane (ITM) region of MIR2 to MIR2-mediated downregulation. Structure prediction and mutagenesis analyses indicate that Phe119 and Ser120 in the MIR2 ITM region and Asp244 in the B7-2 JM region contribute to the recognition of B7-2 by MIR2. This finding provides new insight into the molecular basis of substrate recognition by MIR family members. |
| Databáze: | OpenAIRE |
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