dc.contributor.author |
Tumba, NL
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|
dc.contributor.author |
Naicker, Previn
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|
dc.contributor.author |
Stoychev, Stoyan H
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|
dc.contributor.author |
Killick, MA
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|
dc.contributor.author |
Owen, GR
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|
dc.contributor.author |
Papathanasopoulos, MA
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dc.date.accessioned |
2022-11-06T19:18:42Z |
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dc.date.available |
2022-11-06T19:18:42Z |
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dc.date.issued |
2022-07 |
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dc.identifier.citation |
Tumba, N., Naicker, P., Stoychev, S.H., Killick, M., Owen, G. & Papathanasopoulos, M. 2022. Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics. <i>Biochemical and Biophysical Research Communications, 612.</i> http://hdl.handle.net/10204/12509 |
en_ZA |
dc.identifier.issn |
0006-291X |
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dc.identifier.issn |
1090-2104 |
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dc.identifier.uri |
https://doi.org/10.1016/j.bbrc.2022.04.101
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|
dc.identifier.uri |
doi: 10.1016/j.bbrc.2022.04.101.
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|
dc.identifier.uri |
http://hdl.handle.net/10204/12509
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|
dc.description.abstract |
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) mediates host cell infection by binding to the cellular receptor CD4. Recombinant Env bound to CD4 has been explored for its potential as an HIV vaccine immunogen as receptor binding exposes otherwise shielded, conserved functional sites. Previous preclinical studies showed an interchain disulphide linkage facilitated between Env and 2dCD4S60C generates an immunogenic complex that elicits potent, broadly neutralizing antibodies (bNAbs) against clinically relevant HIV-1. This study investigated conformational dynamics of 2dCD4WT and 2dCD4S60C bound to an HIV-1C SOSIP.664 Env trimer using hydrogen-deuterium exchange mass spectrometry. The Env:2dCD4S60C complex maintains key contact residues required for MHCII and Env/gp120 binding and the residues encompassing Ibalizumab's epitope. Important residues remaining anchored, with an increased flexibility in surrounding regions, evidenced by the higher exchange seen in flanking residues compared to Env:2dCD4WT. While changes in Env:2dCD4S60C dynamics in domain 1 were moderate, domain 2 exhibited greater variation. Lack of stability-inducing H-bonds in these allosteric sites suggest the improved immunogenicity of Env:2dCD4S60C result from exposed CD4 residues providing diverse/novel antigenic targets for the development of potent, broadly neutralizing Ibalizumab-like antibodies. |
en_US |
dc.format |
Abstract |
en_US |
dc.language.iso |
en |
en_US |
dc.relation.uri |
https://www.sciencedirect.com/science/article/pii/S0006291X2200643X?via%3Dihub |
en_US |
dc.relation.uri |
https://pubmed.ncbi.nlm.nih.gov/35550505/ |
en_US |
dc.source |
Biochemical and Biophysical Research Communications, 612 |
en_US |
dc.subject |
Cluster of differentiation 4 |
en_US |
dc.subject |
HIV-1 subtype C SOSIP.664 trimer |
en_US |
dc.subject |
HIV-1 vaccine immunogen |
en_US |
dc.subject |
Hydrogen-deuterium exchange |
en_US |
dc.subject |
Protein dynamics |
en_US |
dc.title |
Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics |
en_US |
dc.type |
Article |
en_US |
dc.description.pages |
181-187 |
en_US |
dc.description.note |
© 2022 Elsevier Inc. All rights reserved. Due to copyright restrictions, the attached PDF file only contains the abstract of the full text item. For access to the full text item, please consult the publisher's website: https://www.sciencedirect.com/science/article/pii/S0006291X2200643X?via%3Dihub |
en_US |
dc.description.cluster |
Next Generation Health |
en_US |
dc.description.impactarea |
Human Molecular Diagnostics |
en_US |
dc.identifier.apacitation |
Tumba, N., Naicker, P., Stoychev, S. H., Killick, M., Owen, G., & Papathanasopoulos, M. (2022). Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics. <i>Biochemical and Biophysical Research Communications, 612</i>, http://hdl.handle.net/10204/12509 |
en_ZA |
dc.identifier.chicagocitation |
Tumba, NL, Previn Naicker, Stoyan H Stoychev, MA Killick, GR Owen, and MA Papathanasopoulos "Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics." <i>Biochemical and Biophysical Research Communications, 612</i> (2022) http://hdl.handle.net/10204/12509 |
en_ZA |
dc.identifier.vancouvercitation |
Tumba N, Naicker P, Stoychev SH, Killick M, Owen G, Papathanasopoulos M. Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics. Biochemical and Biophysical Research Communications, 612. 2022; http://hdl.handle.net/10204/12509. |
en_ZA |
dc.identifier.ris |
TY - Article
AU - Tumba, NL
AU - Naicker, Previn
AU - Stoychev, Stoyan H
AU - Killick, MA
AU - Owen, GR
AU - Papathanasopoulos, MA
AB - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) mediates host cell infection by binding to the cellular receptor CD4. Recombinant Env bound to CD4 has been explored for its potential as an HIV vaccine immunogen as receptor binding exposes otherwise shielded, conserved functional sites. Previous preclinical studies showed an interchain disulphide linkage facilitated between Env and 2dCD4S60C generates an immunogenic complex that elicits potent, broadly neutralizing antibodies (bNAbs) against clinically relevant HIV-1. This study investigated conformational dynamics of 2dCD4WT and 2dCD4S60C bound to an HIV-1C SOSIP.664 Env trimer using hydrogen-deuterium exchange mass spectrometry. The Env:2dCD4S60C complex maintains key contact residues required for MHCII and Env/gp120 binding and the residues encompassing Ibalizumab's epitope. Important residues remaining anchored, with an increased flexibility in surrounding regions, evidenced by the higher exchange seen in flanking residues compared to Env:2dCD4WT. While changes in Env:2dCD4S60C dynamics in domain 1 were moderate, domain 2 exhibited greater variation. Lack of stability-inducing H-bonds in these allosteric sites suggest the improved immunogenicity of Env:2dCD4S60C result from exposed CD4 residues providing diverse/novel antigenic targets for the development of potent, broadly neutralizing Ibalizumab-like antibodies.
DA - 2022-07
DB - ResearchSpace
DP - CSIR
J1 - Biochemical and Biophysical Research Communications, 612
KW - Cluster of differentiation 4
KW - HIV-1 subtype C SOSIP.664 trimer
KW - HIV-1 vaccine immunogen
KW - Hydrogen-deuterium exchange
KW - Protein dynamics
LK - https://researchspace.csir.co.za
PY - 2022
SM - 0006-291X
SM - 1090-2104
T1 - Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics
TI - Covalent binding of human two-domain CD4 to an HIV-1 subtype C SOSIP.664 trimer modulates its structural dynamics
UR - http://hdl.handle.net/10204/12509
ER -
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en_ZA |
dc.identifier.worklist |
26038 |
en_US |