Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Structure. 2023 Oct 5;31(10):1233-1246.e5. doi: 10.1016/j.str.2023.07.009. Epub 2023 Aug 11.
HIV-1 Rev is an essential regulatory protein that transports unspliced and partially spliced viral mRNAs from the nucleus to the cytoplasm for the expression of viral structural proteins. During its nucleocytoplasmic shuttling, Rev interacts with several host proteins to use the cellular machinery for the advantage of the virus. Here, we report the 3.5 Å cryo-EM structure of a 4.8 MDa Rev-tubulin ring complex. Our structure shows that Rev's arginine-rich motif (ARM) binds to both the acidic surfaces and the C-terminal tails of α/β-tubulin. The Rev-tubulin interaction is functionally homologous to that of kinesin-13, potently destabilizing microtubules at sub-stoichiometric levels. Expression of Rev in astrocytes and HeLa cells shows that it can modulate the microtubule cytoskeleton within the cellular environment. These results show a previously undefined regulatory role of Rev.
HIV-1 Rev 是一种必需的调节蛋白，可将未剪接和部分剪接的病毒 mRNA 从细胞核转运到细胞质，以表达病毒结构蛋白。在核质穿梭过程中，Rev 与几种宿主蛋白相互作用，利用细胞机制为病毒带来优势。在这里，我们报告了一个 4.8 MDa Rev-微管环复合物的 3.5 Å 冷冻电镜结构。我们的结构表明，Rev 的富含精氨酸的基序（ARM）与 α/β-微管的酸性表面和 C 端尾部结合。Rev-微管的相互作用在功能上与驱动蛋白-13 同源，在亚化学计量水平上强烈破坏微管。Rev 在星形胶质细胞和 HeLa 细胞中的表达表明，它可以在细胞环境中调节微管细胞骨架。这些结果表明 Rev 具有以前未定义的调节作用。
