5IFA

Crystal structure of unbound VRC01c-HuGL2 Fab from an HIV-1 naive donor at 1.82 A

Summary for 5IFA

• Entry DOI: 10.2210/pdb5ifa/pdb
• Related: 5IES 5IF0
• Descriptor: VRC01c-HuGL2 Fab heavy chain, VRC01c-HuGL2 Fab light chain, SULFATE ION, ... (6 entities in total)
• Functional Keywords: vrc01-class naive human germline antibody, cd4 binding site, immune system, anti-hiv-1
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 49316.88

Authors

Sarkar, A.,Wilson, I.A. (deposition date: 2016-02-25, release date: 2016-04-06, Last modification date: 2023-09-27)

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 (1.821 Å)