Cryo-EM Structure of a Native, Fully Glycosylated, Cleaved HIV-1 Envelope Trimer

The envelope glycoprotein trimer (Env) on the surface of HIV-1 recognizes CD4+ T cells and mediates viral entry. During this process, Env undergoes substantial conformational rearrangements, making it difficult to study in its native state. Soluble stabilized trimers have provided valuable insights into the Env structure, but they lack the hydrophobic membrane proximal external region (an important target of broadly neutralizing antibodies), the transmembrane domain, and the cytoplasmic tail.

A cryogenic electron microscopy (cryo-EM) structure of a clade B virus Env, is provided at a 4.2 Ang. Resolution. Only the cytoplasmic tail is lacking. A reconstruction of this form of Env is given, in complex with broadly neutralizing antibody and Membrane-Proximal-External-Region-targeting antibody at a resolution of 8.8 angstroms. Newly revealed glycans are among the insights provided by these structures in the wild-type Env trimer.