4JPK

Crystal structure of the germline-targeting HIV-1 gp120 engineered outer domain eOD-GT6 in complex with a putative VRC01 germline precursor Fab

Summary for 4JPK

• Entry DOI: 10.2210/pdb4jpk/pdb
• Related: 4JPI 4JPJ
• Descriptor: Putative VRC01 germline precursor Fab heavy chain, Putative VRC01 germline precursor Fab light chain, Germline-targeting HIV-1 gp120 engineered outer domain, eOD-GT6, ... (5 entities in total)
• Functional Keywords: hiv-1 gp120, cd4 binding, vrc01-like broadly neutralizing antibodies, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 68596.35

Authors

Julien, J.-P.,Jardine, J.,Schief, W.R.,Wilson, I.A. (deposition date: 2013-03-19, release date: 2013-04-10, Last modification date: 2024-10-16)

Primary citation

Jardine, J.,Julien, J.P.,Menis, S.,Ota, T.,Kalyuzhniy, O.,McGuire, A.,Sok, D.,Huang, P.S.,MacPherson, S.,Jones, M.,Nieusma, T.,Mathison, J.,Baker, D.,Ward, A.B.,Burton, D.R.,Stamatatos, L.,Nemazee, D.,Wilson, I.A.,Schief, W.R.
Rational HIV immunogen design to target specific germline B cell receptors.
Science, 340:711-716, 2013

PubMed Abstract: Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.

PubMed: 23539181
DOI: 10.1126/science.1234150

Experimental method

X-RAY DIFFRACTION (2.4 Å)