第41页
病毒进入
病毒包膜
脂质双层融合
变构调节
趋化因子受体
糖蛋白
三聚体
生物物理学
细胞生物学
化学
跨膜蛋白
趋化因子受体CCR5
生物
膜
受体
病毒学
病毒复制
病毒
生物化学
趋化因子
表位
抗体
遗传学
有机化学
二聚体
作者
Md Munan Shaik,Hanqin Peng,Jianming Lü,Sophia Rits‐Volloch,Chen Xu,Maofu Liao,Bing Chen
出处
期刊:Nature
[Springer Nature]
日期:2018-12-12
卷期号:565 (7739): 318-323
被引量:161
标识
DOI:10.1038/s41586-018-0804-9
摘要
HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160)3 cleaved to (gp120 and gp41)3, interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents.
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