Crystal structure of a soluble cleaved HIV-1 envelope trimer

Area of Science:

• Structural Biology
• Immunology
• Virology

Background:

• HIV-1 entry relies on cleaved envelope glycoprotein (Env) trimers, which are structurally complex and difficult to study.
• Understanding Env structure is crucial for developing effective HIV vaccines and therapeutics.

Purpose of the Study:

• To determine the high-resolution crystal structure of a stabilized, near-native HIV-1 Env trimer.
• To visualize the interaction between the Env trimer and a broadly neutralizing antibody (PGT122).
• To provide insights for structure-based HIV vaccine design.

Main Methods:

• X-ray crystallography was used to determine the structure of the BG505 SOSIP.664 gp140 trimer in complex with PGT122.
• The structure was resolved at an atomic resolution of 4.7 angstroms.

Main Results:

• The crystal structure reveals a prefusion state of the gp41 component within the Env trimer.
• It elucidates the interactions between gp120 and gp41 subunits, highlighting the stabilizing role of gp120 V1/V2/V3 loops.
• The complete epitope for the broadly neutralizing antibody PGT122 was mapped to gp120 V1, V3, and associated glycans.

Conclusions:

• The solved structure advances the understanding of HIV-1 Env function and its presentation to the immune system.
• This structural information serves as a blueprint for rational, structure-based HIV vaccine development.