5IDL

Crystal structure of the germline-targeting HIV-1 gp120 engineered outer domain, eOD-GT8

Summary for 5IDL

• Entry DOI: 10.2210/pdb5idl/pdb
• Descriptor: Germline-targeting HIV-1 gp120 engineered outer domain, eOD-GT8, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: hiv env, germline-targeting immunogen, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 20173.57

Authors

Julien, J.P.,Ereno-Orbea, J.,Jardine, J.G.,Schief, W.R.,Wilson, I.A. (deposition date: 2016-02-24, release date: 2016-10-05, Last modification date: 2024-11-13)

Primary citation

Jardine, J.G.,Kulp, D.W.,Havenar-Daughton, C.,Sarkar, A.,Briney, B.,Sok, D.,Sesterhenn, F.,Ereno-Orbea, J.,Kalyuzhniy, O.,Deresa, I.,Hu, X.,Spencer, S.,Jones, M.,Georgeson, E.,Adachi, Y.,Kubitz, M.,deCamp, A.C.,Julien, J.P.,Wilson, I.A.,Burton, D.R.,Crotty, S.,Schief, W.R.
HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.
Science, 351:1458-1463, 2016

PubMed 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 naïve 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 naïve 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.

PubMed: 27013733
DOI: 10.1126/science.aad9195

Experimental method

X-RAY DIFFRACTION (2.9 Å)