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| Title | Structural basis of coreceptor recognition by HIV-1 envelope spike. |
|---|---|
| Journal, issue, pages | Nature, Vol. 565, Issue 7739, Page 318-323, Year 2019 |
| Publish date | Dec 12, 2018 |
Authors | Md Munan Shaik / Hanqin Peng / Jianming Lu / Sophia Rits-Volloch / Chen Xu / Maofu Liao / Bing Chen / ![]() |
| PubMed Abstract | HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse ...HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160) cleaved to (gp120 and gp41), 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. |
External links | Nature / PubMed:30542158 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.9 - 4.5 Å |
| Structure data | |
| Chemicals | ![]() ChemComp-NAG: ![]() ChemComp-BMA: ![]() ChemComp-A2G: |
| Source |
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Keywords | MEMBRANE PROTEIN / HIV coreceptor |
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human immunodeficiency virus 1
homo sapiens (human)
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