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The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion

BACKGROUND: The HIV-1 envelope glycoprotein gp120, which mediates viral attachment to target cells, consists for ~50% of sugar, but the role of the individual sugar chains in various aspects of gp120 folding and function is poorly understood. Here we studied the role of the carbohydrate at position...

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Autores principales: Sanders, Rogier W, van Anken, Eelco, Nabatov, Alexei A, Liscaljet, I Marije, Bontjer, Ilja, Eggink, Dirk, Melchers, Mark, Busser, Els, Dankers, Martijn M, Groot, Fedde, Braakman, Ineke, Berkhout, Ben, Paxton, William A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262092/
https://www.ncbi.nlm.nih.gov/pubmed/18237398
http://dx.doi.org/10.1186/1742-4690-5-10
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author Sanders, Rogier W
van Anken, Eelco
Nabatov, Alexei A
Liscaljet, I Marije
Bontjer, Ilja
Eggink, Dirk
Melchers, Mark
Busser, Els
Dankers, Martijn M
Groot, Fedde
Braakman, Ineke
Berkhout, Ben
Paxton, William A
author_facet Sanders, Rogier W
van Anken, Eelco
Nabatov, Alexei A
Liscaljet, I Marije
Bontjer, Ilja
Eggink, Dirk
Melchers, Mark
Busser, Els
Dankers, Martijn M
Groot, Fedde
Braakman, Ineke
Berkhout, Ben
Paxton, William A
author_sort Sanders, Rogier W
collection PubMed
description BACKGROUND: The HIV-1 envelope glycoprotein gp120, which mediates viral attachment to target cells, consists for ~50% of sugar, but the role of the individual sugar chains in various aspects of gp120 folding and function is poorly understood. Here we studied the role of the carbohydrate at position 386. We identified a virus variant that had lost the 386 glycan in an evolution study of a mutant virus lacking the disulfide bond at the base of the V4 domain. RESULTS: The 386 carbohydrate was not essential for folding of wt gp120. However, its removal improved folding of a gp120 variant lacking the 385–418 disulfide bond, suggesting that it plays an auxiliary role in protein folding in the presence of this disulfide bond. The 386 carbohydrate was not critical for gp120 binding to dendritic cells (DC) and DC-mediated HIV-1 transmission to T cells. In accordance with previous reports, we found that N386 was involved in binding of the mannose-dependent neutralizing antibody 2G12. Interestingly, in the presence of specific substitutions elsewhere in gp120, removal of N386 did not result in abrogation of 2G12 binding, implying that the contribution of N386 is context dependent. Neutralization by soluble CD4 and the neutralizing CD4 binding site (CD4BS) antibody b12 was significantly enhanced in the absence of the 386 sugar, indicating that this glycan protects the CD4BS against antibodies. CONCLUSION: The carbohydrate at position 386 is not essential for protein folding and function, but is involved in the protection of the CD4BS from antibodies. Removal of this sugar in the context of trimeric Env immunogens may therefore improve the elicitation of neutralizing CD4BS antibodies.
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spelling pubmed-22620922008-03-04 The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion Sanders, Rogier W van Anken, Eelco Nabatov, Alexei A Liscaljet, I Marije Bontjer, Ilja Eggink, Dirk Melchers, Mark Busser, Els Dankers, Martijn M Groot, Fedde Braakman, Ineke Berkhout, Ben Paxton, William A Retrovirology Research BACKGROUND: The HIV-1 envelope glycoprotein gp120, which mediates viral attachment to target cells, consists for ~50% of sugar, but the role of the individual sugar chains in various aspects of gp120 folding and function is poorly understood. Here we studied the role of the carbohydrate at position 386. We identified a virus variant that had lost the 386 glycan in an evolution study of a mutant virus lacking the disulfide bond at the base of the V4 domain. RESULTS: The 386 carbohydrate was not essential for folding of wt gp120. However, its removal improved folding of a gp120 variant lacking the 385–418 disulfide bond, suggesting that it plays an auxiliary role in protein folding in the presence of this disulfide bond. The 386 carbohydrate was not critical for gp120 binding to dendritic cells (DC) and DC-mediated HIV-1 transmission to T cells. In accordance with previous reports, we found that N386 was involved in binding of the mannose-dependent neutralizing antibody 2G12. Interestingly, in the presence of specific substitutions elsewhere in gp120, removal of N386 did not result in abrogation of 2G12 binding, implying that the contribution of N386 is context dependent. Neutralization by soluble CD4 and the neutralizing CD4 binding site (CD4BS) antibody b12 was significantly enhanced in the absence of the 386 sugar, indicating that this glycan protects the CD4BS against antibodies. CONCLUSION: The carbohydrate at position 386 is not essential for protein folding and function, but is involved in the protection of the CD4BS from antibodies. Removal of this sugar in the context of trimeric Env immunogens may therefore improve the elicitation of neutralizing CD4BS antibodies. BioMed Central 2008-01-31 /pmc/articles/PMC2262092/ /pubmed/18237398 http://dx.doi.org/10.1186/1742-4690-5-10 Text en Copyright © 2008 Sanders et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Sanders, Rogier W
van Anken, Eelco
Nabatov, Alexei A
Liscaljet, I Marije
Bontjer, Ilja
Eggink, Dirk
Melchers, Mark
Busser, Els
Dankers, Martijn M
Groot, Fedde
Braakman, Ineke
Berkhout, Ben
Paxton, William A
The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title_full The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title_fullStr The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title_full_unstemmed The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title_short The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion
title_sort carbohydrate at asparagine 386 on hiv-1 gp120 is not essential for protein folding and function but is involved in immune evasion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2262092/
https://www.ncbi.nlm.nih.gov/pubmed/18237398
http://dx.doi.org/10.1186/1742-4690-5-10
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