9OGU

HIV-1 Env BG505 SOSIP.664-dPG-His in complex with PGT122 and 3BNC117 Fabs

Summary for 9OGU

• Entry DOI: 10.2210/pdb9ogu/pdb
• EMDB information: 70476
• Descriptor: HIV-1 Envelope Glycoprotein BG505 SOSIP.664 gp120, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (15 entities in total)
• Functional Keywords: broadly neutralizing antibody, gp140, vaccine design, stabilizing mutations, protein design, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 18
• Total formula weight: 540130.40

Authors

Andrade, T.G.,Ozorowski, G.,Ward, A.B. (deposition date: 2025-05-01, release date: 2025-08-27, Last modification date: 2025-10-08)

Primary citation

Chaturbhuj, D.N.,Sliepen, K.,Cupo, A.,Steinberg, B.,Kazimierczyk, S.,Munawar, T.,Kramer, K.,Yasmeen, A.,Andrade, T.G.,Lee, W.-H.,van der Maas, L.,Gibson, G.,Feliciano, O.,Del Moral Sanchez, I.,Schermer, E.,Bronson, R.,Benner, A.,Prabhakaran, M.,Mason, R.,Klasse, P.J.,Ward, A.B.,Ozorowski, G.,Sanders, R.W.,Moore, J.P.
A modification to heptad repeat 1 of gp41 improves yield and/or quality of soluble pre-fusion HIV-1 envelope glycoprotein trimers.
J.Virol., 99:e0091325-e0091325, 2025

PubMed Abstract: Native-like HIV-1 envelope glycoprotein (Env) trimers, exemplified by the SOSIP design, are widely used as immunogens, analytical antigens, and for structural studies. These vaccine research and development programs require trimers that are based on multiple HIV-1 genotypes. While a wide range of protein engineering strategies can produce SOSIP trimers from most Env gene sequences, there are still examples of trimers that are expressed only at impractically low yields or that are unstable. Accordingly, additional protein modifications aimed at overcoming such limitations need to be evaluated. Here, we describe a new heptad repeat 1 modification of gp41, known as dPG, that helps to further stabilize the gp41 component of prototypic and germline-targeting SOSIP trimers in the pre-fusion state and thereby increases post-purification yields substantially. The dPG modification involves a deletion (d) at the highly conserved 566 position that disrupts the heptad repeat and introduces proline (P) and glycine (G) substitutions at positions 567 and 568, respectively. We show that the dPG strategy reinforces previously described stabilization changes in existing SOSIP trimers and can rescue otherwise problematic trimer constructs. The latter includes trimers used to target or analyze human germline antibodies and others derived from the global HIV-1 neutralization panel. In summary, the dPG modification strategy can increase the yield and/or quality of Env trimers that are otherwise difficult to produce.

PubMed: 40862550
DOI: 10.1128/jvi.00913-25

Experimental method

ELECTRON MICROSCOPY (3.2 Å)