5JSA

Uncleaved prefusion optimized gp140 trimer with an engineered 10-residue HR1 turn bound to broadly neutralizing antibodies 8ANC195 and PGT128

Summary for 5JSA

• Entry DOI: 10.2210/pdb5jsa/pdb
• Related: 5JS9
• Descriptor: broadly neutralizing antibody PGT128 heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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-(1-2)-alpha-D-mannopyranose-(1-2)-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, ... (16 entities in total)
• Functional Keywords: hiv-1 trimer, ufo, sosip, vaccine, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 180365.45

Authors

Kong, L.,Wilson, I.A. (deposition date: 2016-05-07, release date: 2016-07-13, Last modification date: 2024-10-16)

Primary citation

Kong, L.,He, L.,de Val, N.,Vora, N.,Morris, C.D.,Azadnia, P.,Sok, D.,Zhou, B.,Burton, D.R.,Ward, A.B.,Wilson, I.A.,Zhu, J.
Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability.
Nat Commun, 7:12040-12040, 2016

PubMed Abstract: The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.

PubMed: 27349805
DOI: 10.1038/ncomms12040

Experimental method

X-RAY DIFFRACTION (6.308 Å)