PDBsum entry 5idl

Viral protein

PDB id: 5idl

Contents

Protein chain

162 a.a.

Ligands

NAG ×2

PDB id:

5idl

Name:

Viral protein

Title:

Crystal structure of the germline-targeting HIV-1 gp120 engineered outer domain, eod-gt8

Structure:

Germline-targeting HIV-1 gp120 engineered outer domain, eod-gt8. Chain: a. Engineered: yes

Source:

Human immunodeficiency virus 1. Organism_taxid: 11676. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

2.90Å R-factor: 0.258 R-free: 0.297

Authors:

J.P.Julien,J.Ereno-Orbea,J.G.Jardine,W.R.Schief,I.A.Wilson

Key ref:

J.G.Jardine et al. (2016). HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science, 351, 1458-1463. PubMed id: 27013733 DOI: 10.1126/science.aad9195

Date:

24-Feb-16 Release date: 05-Oct-16

Protein chain

No UniProt id for this chain

Struc: 162 a.a.

DOI no: 10.1126/science.aad9195

Science 351:1458-1463 (2016)

PubMed id: 27013733

HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.

J.G.Jardine, D.W.Kulp, C.Havenar-Daughton, A.Sarkar, B.Briney, D.Sok, F.Sesterhenn, J.Ereño-Orbea, O.Kalyuzhniy, I.Deresa, X.Hu, S.Spencer, M.Jones, E.Georgeson, Y.Adachi, M.Kubitz, A.C.deCamp, J.P.Julien, I.A.Wilson, D.R.Burton, S.Crotty, W.R.Schief.

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.