BACULOVIRUS UBIQUITIN AND THE HOST UBIQUITIN SYSTEM

杆状病毒泛素和宿主泛素系统

• 批准号: 3303220
• 负责人: Linda A. Guarino
• 金额: $ 12.67万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3303220
• 关键词: aminoacid; cell fusion; eukaryote; genetic transcription; genome; hybrid antibody; immunocytochemistry; insect virus; laboratory mouse; laboratory rabbit; monoclonal antibody; mutant; protein sequence; protein structure function; ubiquitin; virus morphology; virus protein

The baculovirus Autographa californica nuclear polyhedrosis virus potentially encodes approximately 100 proteins. One of these proteins has high homology to the eukaryotic protein ubiquitin. Ubiquitin is an abundant protein that participates in or regulates a number of important cell processes. Ubiquitin is highly conserved and varies by only three amino acids between mammals, yeast and plants. It is believed that this conservation of sequence is mandated by the multiple function of ubiquitin. The viral protein, however, differs from mammalian ubiquitin at 18 amino acid residues, although many of the residues known to be essential for ubiquitin function have been conserved. The genomic structure of viral ubiquitin is also unique in that the viral gene encodes a monoubiquitin protein whereas all other ubiquitin genes described so far encode polyproteins or fusion proteins. These observations raise interesting questions with respect to why the viral protein has diverged from eukaryotic ubiquitin and why the virus encodes its own ubiquitin gene when ubiquitin is already present in the host cell. The basic goal of this project is to answer the following question: What is the function of viral ubiquitin and how is that function related to the amino acid sequence? One possibility is that the viral protein has a unique function, for example it could inhibit the host ubiquitin ligation system, disrupting many normal cell functions. Alternatively the viral protein may function in some, but not all, of the roles normally associated with ubiquitin, thereby relieving the evolutionary pressure to maintain the canonical sequence. We intend to address these questions through the use of monoclonal antibodies specific for the host and viral ubiquitins; construction of ubiquitin-deficient viral mutants; and in vitro assays of ubiquitin function using purified viral and host proteins.

杆状病毒副本加州核多面病毒病毒 潜在地编码约100种蛋白质。 这些蛋白质之一具有 与真核蛋白泛素同源。 泛素是一个 参与或调节许多重要的大量蛋白质 细胞过程。 泛素是高度保守的，只有三个 哺乳动物，酵母和植物之间的氨基酸。 相信这个 序列的保护由泛素的多重功能强制。 然而，病毒蛋白与18氨基的哺乳动物泛素不同 酸残基，尽管许多已知的残基对 泛素功能已得到保存。 病毒的基因组结构 泛素也是独一无二的，因为病毒基因编码单喹蛋白 蛋白质，而到目前为止描述的所有其他泛素基因 多蛋白或融合蛋白。 这些观察结果很有趣 关于为什么病毒蛋白与 真核生物泛素以及为什么病毒编码自己的泛素基因时为什么 泛素已经存在于宿主细胞中。 这个基本目标 项目是回答以下问题：病毒的功能是什么 泛素以及该功能与氨基酸序列有何关系？ 一 可能性是病毒蛋白具有独特的功能，例如 可以抑制宿主的泛素连接系统，破坏许多正常 细胞功能。 或者，病毒蛋白可能在某些人中起作用，但是 并非全部，通常与泛素相关的角色，从而缓解 维持规范序列的进化压力。 我们打算 通过使用单克隆抗体特定的解决这些问题 对于宿主和病毒泛素；泛素缺陷的结构 病毒突变体；并使用纯化的泛素功能进行体外测定 病毒和宿主蛋白。