5A8H

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

Summary for 5A8H

• Entry DOI: 10.2210/pdb5a8h/pdb
• Related: 5A7X
• EMDB information: 3096
• Descriptor: HIV-1 GP120, T-CELL SURFACE GLYCOPROTEIN CD4, FAB OF BROADLY NEUTRALIZING ANTIBODY 17B, ... (7 entities in total)
• Functional Keywords: viral protein-immune system complex, virus, viral protein/immune system
• Biological source: HUMAN IMMUNODEFICIENCY VIRUS 1 (HIV-1); More
• Total number of polymer chains: 18
• Total formula weight: 468133.83

Authors

Scharf, L.,Wang, H.,Gao, H.,Chen, S.,McDowall, A.,Bjorkman, P. (deposition date: 2015-07-15, release date: 2015-08-05, Last modification date: 2024-11-06)

Primary citation

Scharf, L.,Wang, H.,Gao, H.,Chen, S.,McDowall, A.W.,Bjorkman, P.J.
Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env.
Cell, 162:1379-1390, 2015

PubMed 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.

PubMed: 26359989
DOI: 10.1016/j.cell.2015.08.035

Experimental method

ELECTRON MICROSCOPY (23 Å)