4JDT: Crystal Structure Of Chimeric Germ-line Precursor Of Nih45-46 Fab In Complex With Gp120 Of 93th057 Hiv-1

Citation:
Abstract
Efforts to design an effective antibody-based vaccine against HIV-1 would benefit from understanding how germ-line B-cell receptors (BCRs) recognize the HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site on gp120. A bottleneck for design of immunogens capable of eliciting PVL antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer domain, including all PVL signature and CD4 mimicry interactions, but not critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are responsible for the improved potency of NIH45-46 over closely related clonal variants, such as VRC01. Our results provide insight into initial recognition of HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens tailored to engage and stimulate broad and potent CD4 binding site antibodies.
PDB ID: 4JDTDownload
MMDB ID: 108520
PDB Deposition Date: 2013/2/25
Updated in MMDB: 2013/05
Experimental Method:
x-ray diffraction
Resolution: 3.26  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4JDT: trimeric; determined by author
Molecular Components in 4JDT
Label Count Molecule
Proteins (3 molecules)
1
Gp120
Molecule annotation
1
FAB Heavy Chain
Molecule annotation
1
FAB Light Chain
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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