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Updated: Jan 16, 2026

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Published on: March 10, 2018

通过CXCR4介导识别HIV包膜尖峰和通过CXCL12抑制

Zhiying Zhang¹, Hongwei Zhang², Lyuqin Zheng³

¹Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. zhangz7@mskcc.org.

Nature communications

|September 30, 2025

概括

研究人员使用冷EM研究HIV-2如何使用CXCR4共受体,发现CXCL12结合抑制了进入. 这揭示了开发针对共同受体相互作用的新HIV治疗方法的结构细节.

科学领域:

结构生物学结构生物学
病毒学病毒学
免疫学免疫学免疫学

背景情况:

CCR5和CXCR4是HIV关键的共同受体,而CXCR4的理解较少.
CXCR4与CXCL12结合,调节细胞功能和HIV的进入,而CXCL12本身则会抑制这种进入.

研究的目的:

通过使用冷电子显微镜 (cryo-EM) 来研究CXCR4对HIV-2包裹 (Env) 尖端识别.
阐明CXCL12在由CXCR4介导的HIV-2进入时的抑制机制.

主要方法:

低温电子显微镜 (cryo-EM) 用于单独确定CXCR4的结构,以及与CXCL12和HIV-2 gp120复合的结构.
分子对接分析以研究HIV抗体机制.

主要成果:

在apo和复杂状态中,CXCR4形成了一个意想不到的四聚体.
CXCR4将CXCL12与4:8和8:8的静态度结合在一起,CXCL12的N端进入CXCR4口袋.
艾滋病毒-2 gp120与CXCR4四聚合物结合,V3循环在受体口袋内深度相互作用;CXCL12结合抑制了这种相互作用.

结论:

CXCL12的N端与HIV-2 gp120 V3循环发生物理冲突,解释了其抑制作用.
对CXCR4-gp120相互作用的结构洞察力有助于理解共受体特异性和切换.
这些发现为设计针对HIV共受体相互作用的新疗法提供了基础.

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