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TitleBroadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env.
Journal, issue, pagesCell, Vol. 162, Issue 6, Page 1379-1390, Year 2015
Publish dateSep 10, 2015
AuthorsLouise Scharf / Haoqing Wang / Han Gao / Songye Chen / Alasdair W McDowall / Pamela J Bjorkman /
PubMed AbstractThe 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 ...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.
External linksCell / PubMed:26359989 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging) / EM (tomography) / X-ray diffraction
Resolution3.584 - 23.0 Å
Structure data

3086

5a7x

EMDB-3086, PDB-5a7x:
negative stain EM of BG505 SOSIP.664 in complex with sCD4, 17b, and 8ANC195
Method: EM (single particle) / Resolution: 16.8 Å

3096

5a8h

EMDB-3096, PDB-5a8h:
cryo-ET subtomogram averaging of BG505 SOSIP.664 in complex with sCD4, 17b, and 8ANC195
Method: EM (subtomogram averaging) / Resolution: 23.0 Å

PDB-5cjx:
Crystal structure of 8ANC195 Fab in complex with BG505 SOSIP.664 HIV-1 Env trimer
Method: X-RAY DIFFRACTION / Resolution: 3.584 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX / VIRUS / HIV-1 Env trimer / IG fold / antibody

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