MATRIX AND HIV1 GAG TARGETING

描述：（改编自研究者摘要）本申请 建议研究Gag如何到达等离子体的重要问题 膜的 在PI的初步研究的实验室表明， 除了豆蔻酰化信号MA之外， 有效的病毒颗粒生产和MA核心子域主要 控制Gag膜结合的特异性而不是效率。 初步数据还表明，缺乏高达90%的MA的突变体， 如果Env掺入的缺陷在某些细胞中有效复制， 正确. 本研究的目的是（目的1）确定 MA：Gag膜靶向的动力学和特异性; HIV病毒体膜的独特脂质组成;以及 MA与细胞骨架。 在AIM 2中，肉豆蔻酰化和MA的作用 磷酸化调节N-末端肉豆蔻基的膜插入 MA组（肉豆蔻基转换假说）将使用 复制能力的MA缺失病毒和其他突变体作为工具。

DESCRIPTION: (Adapted From Investigator's Abstract) This application proposes to study the important question of how Gag reaches the plasma membrane. Preliminary studies in the P.I.'s laboratory suggest that, with the exception of the myristylation signal, MA, is entirely dispensable for efficient viral particle production and that the MA core subdomain primarily governs the specificity rather than the efficiency of Gag membrane binding. Preliminary data also indicate that mutants which lack up to 90% of MA can replicate efficiently in certain cells if a defect in Env incorporation is correct. The goals of the study are (AIM 1) to determine the contribution of MA: to the kinetics and specificity of Gag membrane targeting; to the distinct lipid composition of the HIV virion membrane; and to association of MA with the cytoskeleton. In AIM 2, the role of myristylation and MA phosphorylation in regulating membrane insertion of the N-terminal myristyl group of MA (the myristyl switch hypothesis) will be examined using replication-competent MA-deleted viruses and other mutants as tools.