4XBE: Crystal Structure Of Human 4e10 Fab In Complex With Its Peptide Epitope On Hiv-1 Gp41: Crystals Cryoprotected With Sphingomyelin (02:0 Sm (d18:1/2:0))

Citation:
Abstract
Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane lipids, but the antibody regions contacting lipids and its orientation with respect to the viral membrane are unknown. Vaccine immunogens capable of re-eliciting these membrane proximal external region (MPER)-like antibodies may require a lipid component to be successful. We performed a systematic crystallographic study of lipid binding to 4E10 to identify lipids bound by the antibody and the lipid-interacting regions. We identified phosphatidic acid, phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups, while its CDRH3 interacted with the hydrophobic lipid tails. Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies.
PDB ID: 4XBEDownload
MMDB ID: 136129
PDB Deposition Date: 2014/12/16
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 1.76  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4XBE: trimeric; determined by author and by software (PISA)
Molecular Components in 4XBE
Label Count Molecule
Proteins (3 molecules)
1
4e10 FAB Light Chain
Molecule annotation
1
4e10 FAB Heavy Chain
Molecule annotation
1
Peptide Fragment of HIV Glycoprotein (Gp41) Including the Region 671-683 of the Mper
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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