Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein

We describe methods to improve the properties of soluble, cleaved gp140 trimers of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) for use in structural studies and as immunogens. In the absence of nonionic detergents, gp140 of the KNH1144 genotype, terminating at residu...

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Manylion Llyfryddiaeth
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Cyhoeddwyd: American Society for Microbiology 2013
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Vaccines and Antiviral Agents
Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC3754145/
https://ncbi.nlm.nih.gov/pubmed/23824824
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/JVI.01226-13
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id pubmed-3754145
record_format dspace
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Vaccines and Antiviral Agents
spellingShingle Vaccines and Antiviral Agents
Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
topic_facet Vaccines and Antiviral Agents
description We describe methods to improve the properties of soluble, cleaved gp140 trimers of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) for use in structural studies and as immunogens. In the absence of nonionic detergents, gp140 of the KNH1144 genotype, terminating at residue 681 in gp41 (SOSIP.681), has a tendency to form higher-order complexes or aggregates, which is particularly undesirable for structure-based research. We found that this aggregation in the absence of detergent does not involve the V1, V2, or V3 variable regions of gp120. Moreover, we observed that detergent forms micelles around the membrane-proximal external region (MPER) of the SOSIP.681 gp140 trimers, whereas deletion of most of the MPER residues by terminating the gp140 at residue 664 (SOSIP.664) prevented the aggregation that otherwise occurs in SOSIP.681 in the absence of detergent. Although the MPER can contribute to trimer formation, truncation of most of it only modestly reduced trimerization and lacked global adverse effects on antigenicity. Thus, the MPER deletion minimally influenced the kinetics of the binding of soluble CD4 and a CD4-binding site antibody to immobilized trimers, as detected by surface plasmon resonance. Furthermore, the MPER deletion did not alter the overall three-dimensional structure of the trimers, as viewed by negative-stain electron microscopy. Homogeneous and aggregate-free MPER-truncated SOSIP Env trimers are therefore useful for immunogenicity and structural studies.
author_sort Klasse, Per Johan
title Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
title_short Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
title_full Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
title_fullStr Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
title_full_unstemmed Influences on Trimerization and Aggregation of Soluble, Cleaved HIV-1 SOSIP Envelope Glycoprotein
title_sort influences on trimerization and aggregation of soluble, cleaved hiv-1 sosip envelope glycoprotein
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2013
url https://ncbi.nlm.nih.gov/pmc/articles/PMC3754145/
https://ncbi.nlm.nih.gov/pubmed/23824824
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/JVI.01226-13
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