5IDL: Crystal Structure Of The Germline-targeting Hiv-1 Gp120 Engineered Outer Domain, Eod-gt8

Citation:
Abstract
Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.
PDB ID: 5IDLDownload
MMDB ID: 143729
PDB Deposition Date: 2016/2/24
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.9  Å
Source Organism:
Similar Structures:
Biological Unit for 5IDL: monomeric; determined by author and by software (PISA)
Molecular Components in 5IDL
Label Count Molecule
Protein (1 molecule)
1
Germline-targeting Hiv-1 Gp120 Engineered Outer Domain, Eod-gt8
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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