RT Journal Article
SR Electronic
T1 Structural insights into the conformational plasticity of the full-length trimeric HIV-1 envelope glycoprotein precursor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 288472
DO 10.1101/288472
A1 Shijian Zhang
A1 Wei Li Wang
A1 Shuobing Chen
A1 Maolin Lu
A1 Eden P. Go
A1 Robert T. Steinbock
A1 Haitao Ding
A1 Heather Desaire
A1 John C. Kappes
A1 Joseph Sodroski
A1 Youdong Mao
YR 2018
UL http://biorxiv.org/content/early/2018/03/25/288472.abstract
AB The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer mediates viral entry into cells and is the major target for the host antibody response. In infected cells, the mature Env [(gp120/gp41)3] is produced by cleavage of a trimeric gp160 precursor. Proteolytic cleavage decreases Env conformational flexibility, allowing the mature Env to resist antibody binding to conserved elements. The conformational plasticity of the Env precursor skews the humoral immune response towards the elicitation of ineffectual antibodies, contributing to HIV-1 persistence in the infected host. The structural basis for the plasticity of the Env precursor remains elusive. Here we use cryo-electron microscopy to visualize two coexisting conformational states of the full-length Env precursor at nominal resolutions of 5.5 and 8.0 Å. The State-P2 conformation features a three-helix bundle of the gp41 heptad repeat region in the core, but has disordered membrane-interactive regions. State-P1 trimers lack the three-helix bundle and instead retain ordered transmembrane and membrane-proximal external regions embracing a central cavity. Our structural data shed light on the unusual plasticity of the Env precursor and provide new clues to Env immunogen discovery.