7T2P

The Envelope Glycoprotein SIVmac239.K180S SOSIP trimer in complex with 3 copies of the neutralizing antibody K11

Summary for 7T2P

• Entry DOI: 10.2210/pdb7t2p/pdb
• EMDB information: 25621
• Descriptor: Envelope glycoprotein gp120, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: siv, env, vaccine, neutralizing antibody, glycoprotein, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Simian immunodeficiency virus; More
• Total number of polymer chains: 4
• Total formula weight: 167729.87

Authors

Berndsen, Z.T.,Ward, A.B. (deposition date: 2021-12-06, release date: 2022-10-19, Last modification date: 2024-11-20)

Primary citation

Zhao, F.,Berndsen, Z.T.,Pedreno-Lopez, N.,Burns, A.,Allen, J.D.,Barman, S.,Lee, W.H.,Chakraborty, S.,Gnanakaran, S.,Sewall, L.M.,Ozorowski, G.,Limbo, O.,Song, G.,Yong, P.,Callaghan, S.,Coppola, J.,Weisgrau, K.L.,Lifson, J.D.,Nedellec, R.,Voigt, T.B.,Laurino, F.,Louw, J.,Rosen, B.C.,Ricciardi, M.,Crispin, M.,Desrosiers, R.C.,Rakasz, E.G.,Watkins, D.I.,Andrabi, R.,Ward, A.B.,Burton, D.R.,Sok, D.
Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.
Nat Commun, 13:5236-5236, 2022

PubMed Abstract: SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

PubMed: 36068229
DOI: 10.1038/s41467-022-32783-2

Experimental method

ELECTRON MICROSCOPY (3.47 Å)