Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies
Copyright policy )Asymmetric recognition of HIV-1 Envelope trimer by V1V2 loop-targeting antibodies
The HIV-1 envelope (Env) glycoprotein binds to host cell receptors to mediate membrane fusion. The prefusion Env trimer is stabilized by V1V2 loops that interact at the trimer apex. Broadly neutralizing antibodies (bNAbs) against V1V2 loops, exemplified by PG9, bind asymmetrically as a single Fab to the apex of the symmetric Env trimer using a protruding CDRH3 to penetrate the Env glycan shield. Here we characterized a distinct mode of V1V2 epitope recognition by the new bNAb BG1 in which two Fabs bind asymmetrically per Env trimer using a compact CDRH3. Comparisons between cryo-EM structures of Env trimer complexed with BG1 (6.2 Å resolution) and PG9 (11.5 Å resolution) revealed a new V1V2-targeting strategy by BG1. Analyses of the EM structures provided information relevant to vaccine design including molecular details for different modes of asymmetric recognition of Env trimer and a binding model for BG1 recognition of V1V2 involving glycan flexibility.
- California Institute of Technology United States
- University of California, San Francisco United States
- Rockefeller University United States
- Beth Israel Deaconess Medical Center United States
570, Biomedical and clinical sciences, QH301-705.5, Science, Immunology, 610, virus, HIV Antibodies, Antibodies, env Gene Products, Vaccine Related, Immunoglobulin Fab Fragments, biophysics, structural biology, Humans, Biology (General), Neutralizing, Cryo-EM, Biomedical and Clinical Sciences, Prevention, broadly neutralizing antibodies, Q, Cryoelectron Microscopy, R, env Gene Products, Human Immunodeficiency Virus, Health sciences, Biophysics and Structural Biology, Antibodies, Neutralizing, Biological sciences, Good Health and Well Being, Medical Microbiology, Medicine, Immunization, Biochemistry and Cell Biology, Human Immunodeficiency Virus, Human, Protein Binding
570, Biomedical and clinical sciences, QH301-705.5, Science, Immunology, 610, virus, HIV Antibodies, Antibodies, env Gene Products, Vaccine Related, Immunoglobulin Fab Fragments, biophysics, structural biology, Humans, Biology (General), Neutralizing, Cryo-EM, Biomedical and Clinical Sciences, Prevention, broadly neutralizing antibodies, Q, Cryoelectron Microscopy, R, env Gene Products, Human Immunodeficiency Virus, Health sciences, Biophysics and Structural Biology, Antibodies, Neutralizing, Biological sciences, Good Health and Well Being, Medical Microbiology, Medicine, Immunization, Biochemistry and Cell Biology, Human Immunodeficiency Virus, Human, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).45 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!