Abstract: The prototypic design, designated BG505 SOSIP.664, incorporates an intersubunit disulfide bond (SOS) to covalently link the gp120 and gp41 ectodomain (gp41ECTO) subunits and a point substitution, I559P (IP), to further stabilize the gp41ECTO components.
Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET.
Figure: Env expression, processing and virus incorporation for HIV-1BG505 Q23 carrying SOS, I559P and SOS and I559P (SOS&IP) changes were tested by centrifugation of viruses from cell culture supernatants, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol, and western blotting using the antiserum to HIV-1 gp120 (NIH AIDS reagent no.
Figure: Infectivity of HIV-1BG505 Q23 SOS and I559P was measured by a Gaussia Luciferase assay, and normalized to that of wild-type HIV-1BG505 Q23.
Figure: SOS and I559P effects on infectivity and conformational plasticity of sgp140 SOSIP.664.
Figure: b, The structure-stabilizing modifications A501C and
Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus.
Abstract: The envelope protein (Env) contained a flexible glycine linker and I559P mutation.
Method: 1A: the native leader (signal peptide [SP]) was removed and replaced with the human tissue plasminogen activator (TPA) leader sequence, the furin cleavage site was replaced with a flexible linker sequence (FL), and an I548P mutation equivalent to the I559P in the SOSIP trimers was introduced to improve the trimerization of gp41.
Figure: The native signal peptide (HIV-1 SP) was replaced with the human tissue plasminogen activator (TPA SP) sequence, the furin cleavage site (KEKR) was replaced with a flexible linker (FL) sequence, and an I559P mutation was introduced.
Discussion: The flexible linker and PMID: 30557314
2018
PloS one
Result: Finally, the I559P mutation was introduced to stabilise the gp41 trimer thus generating CAP256 SU gp140-FL-IP (afterwards referred to as CAP256 gp140).
Figure: (A) Schematic representation of wild type Env and truncated CAP256 gp140-FL-IP (soluble CAP256 Env) in which the native
Discussion: The structure of Env is important in vaccine studies: accordingly, the antigen in this study was stabilised by replacing the furin cleavage site with a flexible glycine-rich linker, and a I559P mutation.
Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage.
Abstract: This P improved trimer integrity compared to I559P in selected properties.
Introduction: The original NFL trimer design contains the I559P mutation as well to disfavor the post-fusion state.
Introduction: These trimers also contain a I559P substitution in the gp41 heptad repeat 1 (HR1) region to generate well-ordered oligomers and, as well, require expression of exogenous furin for conformational integrity.
Method: The parental NFL contains a proline substitution at residue 559 (I559P) to facilitate trimer formation.
Result: Because the HR1 region is relatively conserved among Env from different clades, we determined whether the P substitutions identified in the BG505 NFL context could be transferred to the clade C 16055 NFL, which is inefficie
SOSIP Changes Affect Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Conformation and CD4 Engagement.
Abstract: Most structural studies of Env trimers have utilized truncated soluble gp140 Envs stabilized with the I559P and SOS changes.
Abstract: The introduction of an artificial disulfide bond linking the gp120 and gp41 subunits (SOS) in combination with the I559P (IP) change has allowed structural characterization of soluble gp140 (sgp140) trimers.
Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains.
Abstract: We used a 96-well expression-screening format to assess the ability of artificial disulfides and Ile559Pro substitution (DS-SOSIP) to produce soluble cleaved-Env trimers; from 180 Env strains, 20 yielded prefusion closed trimers.
Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly neutralizing epitopes including V2 and C2 domain-dependent conformational epitopes.
Introduction: This problem has been circumvented by generating SOSIP versions (containing A501C, T605C, I559P mutations in BG505) of the cleaved, C-terminus truncated Env glycoprotein to aa664 and purifying the trimeric form.
Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers.
Abstract: The addition of a 20-residue flexible linker (FL20) between the gp120 and gp41 ectodomain (gp41ECTO) subunits to make the uncleaved 92UG037.8 gp140-FL20 construct is not sufficient to create a native-like trimer, but a small percentage of native-like trimers were produced when an I559P substitution in gp41ECTO was also present.
Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer.
Abstract: An isoleucine-to-proline change (I559P) in the gp41 ectodomain has been used to stabilize soluble forms of HIV-1 Env trimers for structural characterization and for use as immunogens.
Abstract: Compared with the wild-type Env, the I559P Env was recognized inefficiently by polyclonal sera from HIV-1-infected individuals, by several gp41-directed antibodies, by some antibodies against the CD4-binding site of gp120, and by antibodies that preferentially recognize the CD4-bound Env.
Abstract: In the native membrane-anchored HIV-1BG505 Env, the
HIV mutation literature information.
PMID: 
2019
Journal of virology
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