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TitleAffinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans.
Journal, issue, pagesImmunity, Vol. 43, Issue 6, Page 1053-1063, Year 2015
Publish dateDec 15, 2015
AuthorsFernando Garces / Jeong Hyun Lee / Natalia de Val / Alba Torrents de la Pena / Leopold Kong / Cristina Puchades / Yuanzi Hua / Robyn L Stanfield / Dennis R Burton / John P Moore / Rogier W Sanders / Andrew B Ward / Ian A Wilson /
PubMed AbstractThe high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such ...The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates.
External linksImmunity / PubMed:26682982 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.105 - 22.0 Å
Structure data

EMDB-3092:
BG505 SOSIP.664 trimer in complex with PGT124 Fab with 32H heavy chain
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-3093:
BG505 SOSIP.664 N137A trimer in complex with PGT124 Fab with 3H heavy chain
Method: EM (single particle) / Resolution: 17.0 Å

EMDB-6379:
Electron Microscopy of Bg505 in complex with 9H3L antibody
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-6380:
Bg505 SOSIP N137A in complex with 9H3L antibody
Method: EM (single particle) / Resolution: 19.0 Å

PDB-5cex:
Crystal Structure of Fab 32H+109L, a putative precursor of the PGT121 family of potent HIV-1 antibodies
Method: X-RAY DIFFRACTION / Resolution: 2.105 Å

PDB-5cey:
Crystal Structure of Fab 9H+3L, a putative precursor of the PGT121 family of potent HIV-1 antibodies
Method: X-RAY DIFFRACTION / Resolution: 2.387 Å

PDB-5cez:
Crystal Structure of the BG505 SOSIP gp140 HIV-1 Env trimer in Complex with an early putative precursor of the PGT121 family at 3.0 Angstrom
Method: X-RAY DIFFRACTION / Resolution: 3.031 Å

Chemicals

ChemComp-PG4:
TETRAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-GOL:
GLYCEROL / Glycerol

ChemComp-P6G:
HEXAETHYLENE GLYCOL / precipitant*YM / Polyethylene glycol

ChemComp-PGE:
TRIETHYLENE GLYCOL / Polyethylene glycol

ChemComp-HOH:
WATER / Water

ChemComp-PE7:
1-DEOXY-1-THIO-HEPTAETHYLENE GLYCOL

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

ChemComp-MAN:
alpha-D-mannopyranose / Mannose

Source
  • Human Immunodeficiency Virus-1
  • homo sapiens (human)
  • Simian-Human immunodeficiency virus
  • human immunodeficiency virus 1
KeywordsIMMUNE SYSTEM / HIV-1 / Antibody / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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