Premium
The HIV ‐1 envelope glycoprotein structure: nailing down a moving target
Author(s) -
Ward Andrew B,
Wilson Ian A
Publication year - 2017
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12507
Subject(s) - trimer , glycoprotein , epitope , gp41 , glycan , antibody , virology , biology , neutralizing antibody , protein structure , neutralization , computational biology , microbiology and biotechnology , chemistry , virus , genetics , biochemistry , dimer , organic chemistry
Summary Structure determination of the HIV ‐1 envelope glycoprotein (Env) presented a number of challenges, but several high‐resolution structures have now become available. In 2013, cryo‐ EM and x‐ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG 505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo‐ EM structure of a native full‐length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes. These Env trimers when used as immunogens, have led to the first vaccine‐induced neutralizing antibodies for structural and functional analyses.