AIDS and Cancer Virus Program, National Cancer Institute at Frederick, Frederick, MD, 21702-1201, USA.
Advanced Technology Program, National Cancer Institute at Frederick, Frederick, MD, 21702-1201, USA.
Virology. 2019 Sep;535:272-278. doi: 10.1016/j.virol.2019.07.015. Epub 2019 Jul 19.
The late (L) domain sequence used by mouse mammary tumor virus (MMTV) remains undefined. Similar to other L domain-containing proteins, MMTV p8 and p14 proteins are monoubiquitinated, suggesting L domain function. Site-directed mutagenesis of p8, PLPPV, and p14, PLPPL, sequences in MMTV Gag revealed a requirement only for the PLPPV sequence in virion release in a position-dependent manner. Electron microscopy of a defective Gag mutant confirmed an L domain budding defect morphology. The equine infectious anemia virus (EIAV) YPDL core L domain sequence and PLPPV provided L domain function in reciprocal MMTV and EIAV Gag exchange mutants, respectively. Alanine scanning of the PLPPV sequence revealed a strict requirement for the valine residue but only minor requirements for any one of the other residues. Thus, PLPPV provides MMTV L domain function, representing a fourth type of retroviral L domain that enables MMTV Gag proteins to co-opt cellular budding pathways for release.
鼠乳腺肿瘤病毒(MMTV)使用的晚期(L)结构域序列尚未确定。与其他含有 L 结构域的蛋白质一样,MMTV p8 和 p14 蛋白被单泛素化,表明 L 结构域的功能。对 MMTV Gag 中的 p8、PLPPV 和 p14、PLPPL 序列进行定点突变,发现只有 PLPPV 序列以位置依赖的方式对病毒粒子释放有要求。对有缺陷的 Gag 突变体的电子显微镜检查证实了 L 结构域出芽缺陷的形态。马传染性贫血病毒(EIAV)的 YPDL 核心 L 结构域序列和 PLPPV 分别在相互的 MMTV 和 EIAV Gag 交换突变体中提供了 L 结构域功能。对 PLPPV 序列进行丙氨酸扫描表明,缬氨酸残基的要求非常严格,但其他任何一个残基的要求都很低。因此,PLPPV 提供了 MMTV L 结构域功能,代表了第四种能够使 MMTV Gag 蛋白共同利用细胞出芽途径进行释放的逆转录病毒 L 结构域。