Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield.

ABSTRACT: The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expression due to their inherent metastability, making biochemical and immunological experiments impractical or impossible. Here, we report a novel proline stabilization strategy to facilitate the production of prefusion Env trimers. This approach, termed "2P," works synergistically with previously described SOSIP mutations and dramatically increases the yield of recombinantly expressed Env ectodomains without altering the antigenic or conformational properties of near-native Env. We determined that the 2P mutations function by enhancing the

SUBMITTER: Wrapp D 

PROVIDER: S-EPMC9888283 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature