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TitleStructural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.
Journal, issue, pagesImmunity, Vol. 40, Issue 5, Page 669-680, Year 2014
Publish dateMay 15, 2014
AuthorsClaudia Blattner / Jeong Hyun Lee / Kwinten Sliepen / Ronald Derking / Emilia Falkowska / Alba Torrents de la Peña / Albert Cupo / Jean-Philippe Julien / Marit van Gils / Peter S Lee / Wenjie Peng / James C Paulson / Pascal Poignard / Dennis R Burton / John P Moore / Rogier W Sanders / Ian A Wilson / Andrew B Ward /
PubMed AbstractAll previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a ...All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer.
External linksImmunity / PubMed:24768348 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.827 - 25.0 Å
Structure data

EMDB-5918:
Negative stain reconstruction of PGT151 Fab in complex with BG505 Env with transmembrane region
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-5919:
Negative stain reconstruction of PGT151 Fab in complex with JR-FL Env with transmembrane region
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-5920:
Negative stain reconstruction of PGT151 Fab in complex with cleaved IAVI C22 Env trimer containing the transmembrane region
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-5921:
Negative stain reconstruction of PGT151 Fab in complex with the soluble Env trimer BG505 SOSIP
Method: EM (single particle) / Resolution: 22.0 Å

PDB-4nug:
Crystal structure of HIV-1 broadly neutralizing antibody PGT151
Method: X-RAY DIFFRACTION / Resolution: 1.8617 Å

PDB-4nuj:
Crystal structure of HIV-1 broadly neutralizing antibody PGT152
Method: X-RAY DIFFRACTION / Resolution: 1.827 Å

Chemicals

ChemComp-P6G:
HEXAETHYLENE GLYCOL / precipitant*YM

ChemComp-HOH:
WATER

Source
  • Human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / immunoglobulin / Fab fragment / HIV Envelope

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