4LSV: Crystal Structure Of Broadly And Potently Neutralizing Antibody 3bnc117 In Complex With Hiv-1 Clade C C1086 Gp120

Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.
PDB ID: 4LSVDownload
MMDB ID: 112896
PDB Deposition Date: 2013/7/23
Updated in MMDB: 2013/09
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4LSV: trimeric; determined by author and by software (PISA)
Molecular Components in 4LSV
Label Count Molecule
Proteins (3 molecules)
Envelope Glycoprotein Gp120
Molecule annotation
Heavy Chain of Antibody 3bnc117
Molecule annotation
Light Chain of Antibody 3bnc117
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB