6MEO

Structural basis of coreceptor recognition by HIV-1 envelope spike

Summary for 6MEO

• Entry DOI: 10.2210/pdb6meo/pdb
• EMDB information: 9108
• Descriptor: Envelope glycoprotein gp160, T-cell surface glycoprotein CD4, C-C chemokine receptor type 5, ... (9 entities in total)
• Functional Keywords: hiv coreceptor, membrane protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 113929.36

Authors

Shaik, M.M.,Chen, B. (deposition date: 2018-09-06, release date: 2018-12-12, Last modification date: 2024-10-23)

Primary citation

Shaik, M.M.,Peng, H.,Lu, J.,Rits-Volloch, S.,Xu, C.,Liao, M.,Chen, B.
Structural basis of coreceptor recognition by HIV-1 envelope spike.
Nature, 565:318-323, 2018

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 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.

PubMed: 30542158
DOI: 10.1038/s41586-018-0804-9

Experimental method

ELECTRON MICROSCOPY (3.9 Å)