5IES

Crystal structure of VRC01c-HuGL2 Fab from an HIV-1 naive donor in complex with with a germline-targeting gp120 engineered outer domain eOD-GT8 at 2.16 A

Summary for 5IES

• Entry DOI: 10.2210/pdb5ies/pdb
• Related: 5IF0 5IFA
• Descriptor: VRC01cHuGL2 Fab heavy chain, VRC01cHuGL2 Fab light chain, Germline-targeting HIV-1 gp120 engineered outer domain eOD-GT8, ... (6 entities in total)
• Functional Keywords: hiv-1 gp120, engineered outer domain (eod), germline targeting, cd4 binding site, vrc01-class naive human germline antibody, immune system, viral-protein complex, immune system-viral protein complex, immune system- viral protein complex, immune system/ viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 68038.93

Authors

Sarkar, A.,Wilson, I.A. (deposition date: 2016-02-25, release date: 2016-04-06, Last modification date: 2024-11-20)

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 (2.16 Å)