6WIX

Crystal Structure of HIV-1 MI369 RnS-DS.SOSIP Prefusion Env Trimer in Complex with Human Antibodies 3H109L and 35O22 at 3.5 Angstrom

Summary for 6WIX

• Entry DOI: 10.2210/pdb6wix/pdb
• Descriptor: Envelope glycoprotein gp41, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[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, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: hiv-1 envelope prefusion trimer, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 157613.48

Authors

Lai, Y.-T.,Olia, A.,Kwong, P.D. (deposition date: 2020-04-10, release date: 2020-11-25, Last modification date: 2024-11-20)

Primary citation

Rawi, R.,Rutten, L.,Lai, Y.T.,Olia, A.S.,Blokland, S.,Juraszek, J.,Shen, C.H.,Tsybovsky, Y.,Verardi, R.,Yang, Y.,Zhang, B.,Zhou, T.,Chuang, G.Y.,Kwong, P.D.,Langedijk, J.P.M.
Automated Design by Structure-Based Stabilization and Consensus Repair to Achieve Prefusion-Closed Envelope Trimers in a Wide Variety of HIV Strains.
Cell Rep, 33:108432-108432, 2020

PubMed Abstract: Soluble envelope (Env) trimers, stabilized in a prefusion-closed conformation, can elicit neutralizing responses against HIV-1 strains closely related to the immunizing trimer. However, to date such stabilization has succeeded with only a limited number of HIV-1 strains. To address this issue, here we develop ADROITrimer, an automated procedure involving structure-based stabilization and consensus repair, and generate "RnS-DS-SOSIP"-stabilized Envs from 180 diverse Env sequences. The vast majority of these RnS-DS-SOSIP Envs fold into prefusion-closed conformations as judged by antigenic analysis and size exclusion chromatography. Additionally, representative strains from clades AE, B, and C are stabilized in prefusion-closed conformations as shown by negative-stain electron microscopy, and the crystal structure of a clade A strain MI369.A5 Env trimer provides 3.5 Å resolution detail into stabilization and repair mutations. The automated procedure reported herein that yields well-behaved, soluble, prefusion-closed Env trimers from a majority of HIV-1 strains could have substantial impact on the development of an HIV-1 vaccine.

PubMed: 33238130
DOI: 10.1016/j.celrep.2020.108432

Experimental method

X-RAY DIFFRACTION (2.67 Å)