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BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2
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نویسنده
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harter m.r. ,liu c.-d. ,shen c.-l. ,gonzalez-hurtado e. ,zhang z.-m. ,xu m. ,martinez e. ,peng c.-w. ,song j.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 2
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چکیده
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Epstein-barr virus (ebv) nuclear antigen 2 (ebna2) plays an important role in driving immortalization of ebv-infected b cells through regulating the expression of many viral and cellular genes. we report a structural study of the tumor suppressor bs69/zmynd11 c-terminal region,comprised of tandem coiled-coil-mynd domains (bs69cc-mynd),in complex with an ebna2 peptide containing a pxlxp motif. the coiled-coil domain of bs69 self-associates to bring two separate mynd domains in close proximity,thereby enhancing the bs69 mynd-ebna2 interaction. itc analysis of bs69cc-mynd with a c-terminal fragment of ebna2 further suggests that the bs69cc-mynd homodimer synergistically binds to the two ebna2 pxlxp motifs that are respectively located in the conserved regions cr7 and cr8. furthermore,we showed that ebna2 interacts with bs69 and down-regulates its expression at both mrna and protein levels in ebv-infected b cells. ectopic bs69cc-mynd is recruited to viral target promoters through interactions with ebna2,inhibits ebna2-mediated transcription activation,and impairs proliferation of lymphoblastoid cell lines (lcls). substitution of critical residues in the mynd domain impairs the bs69-ebna2 interaction and abolishes the bs69 inhibition of the ebna2-mediated transactivation and lcl proliferation. this study identifies the bs69 c-terminal domains as an inhibitor of ebna2,which may have important implications in development of novel therapeutic strategies against ebv infection. © 2016 harter et al.
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آدرس
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department of biochemistry,university of california,riverside,riverside,ca, United States, institute of medical sciences,tzu chi university,hualien, Taiwan, institute of medical sciences,tzu chi university,hualien, Taiwan, department of biochemistry,university of california,riverside,riverside,ca,united states,marc u-star program,university of california,riverside,riverside,ca, United States, department of biochemistry,university of california,riverside,riverside,ca, United States, department of biochemistry,university of california,riverside,riverside,ca, United States, department of biochemistry,university of california,riverside,riverside,ca,united states,marc u-star program,university of california,riverside,riverside,ca, United States, institute of medical sciences,tzu chi university,hualien, Taiwan, department of biochemistry,university of california,riverside,riverside,ca, United States
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Authors
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