Structural analysis and therapeutic nanobody development of KSHV G-protein coupled receptor

项目总结/摘要 尽管这是一个紧迫的人类健康问题，但迄今为止， 针对卡波西肉瘤相关疱疹病毒（KSHV）感染及其相关的 疾病有趣的是，KSHV基因组携带细胞G蛋白偶联的病毒同源物， 受体（GPCR）。GPCR作为细胞信号转导的重要介质，参与了细胞信号转导的各个方面 人类生物学。其临床相关性因此强调了以下事实：30-40%的FDA 批准的药物靶向GPCR。KSHV GPCR（vGPCR）对于病毒介导的 肿瘤发生：其表达足以在体外转化细胞并在体内诱导肿瘤形成。 vGPCR在KSHV肿瘤发生中起关键作用，并且是蛋白质家族的一员， FDA批准的药物经常靶向vGPCR，这使得vGPCR成为一种有希望的治疗靶点。 干预我们将使用生物化学方法和信号分析来了解结构的洞察力 并开发用于抑制vGPCR的致癌功能的新型治疗性纳米抗体。 vGPCR。

Project Summary/Abstract Despite being a pressing human health problem, very little has been done thus far to develop specific therapeutics against Kaposi’s sarcoma-associated Herpesvirus (KSHV) infection and its associated diseases. Interestingly, the KSHV genome carries a viral homolog of cellular G-protein coupled receptor (GPCR). As essential mediators of cell signaling, GPCRs are involved in nearly all aspects of human biology. Their clinical relevance is thus underscored by the fact that 30-40% of all FDA approved drugs target GPCRs. The KSHV GPCR (vGPCR) is essential for virus-mediated oncogenesis: its expression is sufficient to transform cells in vitro and induce tumor formation in vivo. The fact that vGPCR plays a key role in KSHV oncogenesis and that it is a member of protein family frequently targeted by FDA-approved drugs makes vGPCR a promising target for therapeutic intervention. We will use biochemical methods and signaling assays to understand structural insight of vGPCR and to develop novel therapeutic nanobodies for inhibiting the oncogenic function of vGPCR.