Montal M
Section of Neurobiology, Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0366, USA.
FEBS Lett. 2003 Sep 18;552(1):47-53. doi: 10.1016/s0014-5793(03)00849-4.
Vpu, a membrane protein from human immunodeficiency virus-1, folds into two distinct structural domains with different biological activities: a transmembrane (TM) helical domain involved in the budding of new virions from infected cells, and a cytoplasmic domain encompassing two amphipathic helices, which is implicated in CD4 degradation. The molecular mechanism by which Vpu facilitates virion budding is not clear. This activity of Vpu requires an intact TM helical domain. And it is known that oligomerization of the VPU TM domain results in the formation of sequence-specific, cation-selective channels. It has been shown that the channel activity of Vpu is confined to the TM domain, and that the cytoplasmic helices regulate the lifetime of the Vpu channel in the conductive state. Structure-function correlates based on the convergence of information about the channel activity of Vpu reconstituted in lipid bilayers and on its 3-D structure in membranes by a combination of solution and solid-state nuclear magnetic resonance spectroscopy may provide valuable insights to understand the role of Vpu in the pathogenesis of AIDS and for drug design aimed to block channel activity.
Vpu是一种来自人类免疫缺陷病毒1型的膜蛋白，可折叠成具有不同生物学活性的两个不同结构域：一个跨膜（TM）螺旋结构域，参与新病毒粒子从受感染细胞中出芽；一个细胞质结构域，包含两个两亲性螺旋，与CD4降解有关。Vpu促进病毒粒子出芽的分子机制尚不清楚。Vpu的这种活性需要完整的TM螺旋结构域。已知VPU TM结构域的寡聚化会导致序列特异性阳离子选择性通道的形成。研究表明，Vpu的通道活性局限于TM结构域，并且细胞质螺旋调节Vpu通道在导电状态下的寿命。基于脂质双层中重组的Vpu通道活性信息与其通过溶液和固态核磁共振光谱相结合得到的膜中三维结构的收敛所建立的结构-功能相关性，可能为理解Vpu在艾滋病发病机制中的作用以及设计旨在阻断通道活性的药物提供有价值的见解。
