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TitleStructural basis of coreceptor recognition by HIV-1 envelope spike.
Journal, issue, pagesNature, Vol. 565, Issue 7739, Page 318-323, Year 2019
Publish dateDec 12, 2018
AuthorsMd Munan Shaik / Hanqin Peng / Jianming Lu / Sophia Rits-Volloch / Chen Xu / Maofu Liao / Bing Chen /
PubMed AbstractHIV-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 linksNature / PubMed:30542158 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 4.5 Å
Structure data

EMDB-9108, PDB-6meo:
Structural basis of coreceptor recognition by HIV-1 envelope spike
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9109, PDB-6met:
Structural basis of coreceptor recognition by HIV-1 envelope spike
Method: EM (single particle) / Resolution: 4.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-BMA:
beta-D-mannopyranose

ChemComp-A2G:
2-acetamido-2-deoxy-alpha-D-galactopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / HIV coreceptor

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