Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Mol Cell. 2010 Mar 12;37(5):656-67. doi: 10.1016/j.molcel.2010.02.012.
The entry of human immunodeficiency virus (HIV-1) into cells is initiated by binding of the gp120 exterior envelope glycoprotein to the receptor, CD4. How does CD4 binding trigger conformational changes in gp120 that allow the gp41 transmembrane envelope glycoprotein to mediate viral-cell membrane fusion? The transition from the unliganded to the CD4-bound state is regulated by two potentially flexible topological layers (layers 1 and 2) in the gp120 inner domain. Both layers apparently contribute to the noncovalent association of unliganded gp120 with gp41. After CD4 makes initial contact with the gp120 outer domain, layer 1-layer 2 interactions strengthen gp120-CD4 binding by reducing the off rate. Layer 1-layer 2 interactions also destabilize the activated state induced on HIV-1 by treatment with soluble CD4. Thus, despite lack of contact with CD4, the gp120 inner-domain layers govern CD4 triggering by participating in conformational transitions within gp120 and regulating the interaction with gp41.
人类免疫缺陷病毒 (HIV-1) 进入细胞是由外膜糖蛋白 gp120 与受体 CD4 的结合引发的。CD4 结合如何触发 gp120 构象变化，使 gp41 跨膜包膜糖蛋白介导病毒-细胞膜融合？未结合状态到 CD4 结合状态的转变受 gp120 内环中两个潜在的灵活拓扑层（层 1 和 2）调节。这两个层显然都有助于未结合的 gp120 与 gp41 的非共价结合。在 CD4 与 gp120 外域最初接触后，层 1-层 2 相互作用通过降低离解速率来增强 gp120-CD4 结合。层 1-层 2 相互作用还会破坏可溶性 CD4 处理后 HIV-1 诱导的激活状态。因此，尽管 gp120 内环没有与 CD4 接触，但通过参与 gp120 内的构象转变和调节与 gp41 的相互作用，内层参与了 CD4 的触发。
