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Trimeric HIV Env provides epitope occlusion mediated by hypervariable loops
- Source :
- Scientific Reports, Scientific Reports, Nature Publishing Group, 2015, 4 (1), ⟨10.1038/srep07025⟩, Scientific reports, vol 4, iss 1, Scientific Reports, 2015, 4 (1), ⟨10.1038/srep07025⟩
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3′ that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.
- Subjects :
- Models, Molecular
Protein Conformation
viruses
Human immunodeficiency virus (HIV)
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Plasma protein binding
HIV Envelope Protein gp120
medicine.disease_cause
Env Protein
Epitope
env Gene Products
Epitopes
Protein structure
Models
ComputingMilieux_MISCELLANEOUS
Sequence Deletion
Genetics
Multidisciplinary
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM]
Transition (genetics)
biology
env Gene Products, Human Immunodeficiency Virus
virus diseases
hypervariable loops
HIV Envelope Protein gp41
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
3. Good health
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
CD4 Antigens
HIV/AIDS
Antibody
Human Immunodeficiency Virus
Protein Binding
Env
Gp41
Article
Vaccine Related
[CHIM.CRIS]Chemical Sciences/Cristallography
medicine
Humans
Protein Interaction Domains and Motifs
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Antigens
Vaccine Related (AIDS)
Prevention
ta1182
Molecular
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
CD4
Peptide Fragments
gp120
Good Health and Well Being
HIV-1
biology.protein
Immunization
Protein Multimerization
protein
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....bc0f75fcc48bcc778a58e2127bd2e1b6