EMD-3096

Subtomogram averaging
23.0 Å
EMD-3096 Deposition: 14/07/2015
Map released: 23/09/2015
Last modified: 23/09/2015
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-3096

cryo-ET subtomogram averaging of BG505 SOSIP.664 in complex with sCD4, 17b, and 8ANC195

EMD-3096

Subtomogram averaging
23.0 Å
EMD-3096 Deposition: 14/07/2015
Map released: 23/09/2015
Last modified: 23/09/2015
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human immunodeficiency virus 1
Sample: soluble HIV-1 Env trimer BG505 SOSIP.664 in complex with soluble CD4s (D1-D2), broadly neutralizing antibody 17b Fabs, and broadly neutralizing antibody 8ANC195 variant G32K5 Fabs
Fitted models: 5a8h (Avg. Q-score: 0.06)

Deposition Authors: Scharf L, Wang H, Gao H, Chen S, McDowall A, Bjorkman P
Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env
Scharf L, Wang H, Gao H, Chen S, McDowall A, Bjorkman P
(2015) Cell , 162 , 1379 - 1390
Abstract:
The HIV-1 envelope (Env) spike contains limited epitopes for broadly neutralizing antibodies (bNAbs); thus, most neutralizing antibodies are strain specific. The 8ANC195 epitope, defined by crystal and electron microscopy (EM) structures of bNAb 8ANC195 complexed with monomeric gp120 and trimeric Env, respectively, spans the gp120 and gp41 Env subunits. To investigate 8ANC195's gp41 epitope at higher resolution, we solved a 3.58 Å crystal structure of 8ANC195 complexed with fully glycosylated Env trimer, revealing 8ANC195 insertion into a glycan shield gap to contact gp120 and gp41 glycans and protein residues. To determine whether 8ANC195 recognizes the CD4-bound open Env conformation that leads to co-receptor binding and fusion, one of several known conformations of virion-associated Env, we solved EM structures of an Env/CD4/CD4-induced antibody/8ANC195 complex. 8ANC195 binding partially closed the CD4-bound trimer, confirming structural plasticity of Env by revealing a previously unseen conformation. 8ANC195's ability to bind different Env conformations suggests advantages for potential therapeutic applications.