Abstract
Human immunodeficiency viral (HIV-1) fusion is mediated by the viral envelope gp120/gp41 complex (ENVelope glycoprotein). After gp120 shedding, gp41 is exposed and elicits membrane fusion via a cascade of conformational changes. In contrast to prefusion and postfusion conformation, little is known about any intermediate conformation. We report on a solution NMR investigation of homotrimeric HIV-1 gp41(27-194), comprising the transmembrane region and reconstituted in dodecyl phosphocholine (DPC) micelles. The protein is mainly ?-helical, but experiences internal dynamics on the nanosecond and micro to millisecond time scale and transient ?-helical behavior for certain residues in the N-terminal heptad repeat (NHR). Strong lipid interactions are observed, in particular for C-terminal residues of the NHR and imunodominant loop region connecting NHR and C-terminal heptad repeat (CHR). Our data indicate an extended conformation with features anticipated for a prefusion intermediate, presumably in exchange with a lowly populated postfusion six-helical bundle conformation.
PMID: 25132083 [PubMed - as supplied by publisher]
HIV-1 Envelope Protein gp41: An NMR Study of Dodecyl Phosphocholine Embedded gp41 Reveals a Dynamic Prefusion Intermediate Conformation
HIV-1 Envelope Protein gp41: An NMR Study of Dodecyl Phosphocholine Embedded gp41 Reveals a Dynamic Prefusion Intermediate Conformation
Publication date: Available online 14 August 2014
Source:Structure</br>
Author(s): Nils-Alexander Lakomek , Joshua*D. Kaufman , Stephen*J. Stahl , Paul*T. Wingfield</br>
Human immunodeficiency viral (HIV-1) fusion is mediated by the viral envelope gp120/gp41 complex (ENVelope glycoprotein). After gp120 shedding, gp41 is exposed and elicits membrane fusion via a cascade of conformational changes. In contrast to prefusion and...
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08-14-2014 09:44 PM
[NMR paper] Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel ? sheet fusion peptide structure in the final six-helix bundle state.
Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel ? sheet fusion peptide structure in the final six-helix bundle state.
Related Articles Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel ? sheet fusion peptide structure in the final six-helix bundle state.
J Mol Biol. 2013 Nov 15;
Authors: Sackett K, Nethercott MJ, Zheng Z, Weliky DP
Abstract
The HIV gp41 protein catalyzes fusion between viral and target cell membranes. Although...
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11-20-2013 12:52 PM
Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel ? sheet fusion peptide structure in the final six-helix bundle state
Solid-state NMR spectroscopy of the HIV gp41 membrane fusion protein supports intermolecular antiparallel ? sheet fusion peptide structure in the final six-helix bundle state
Publication date: Available online 16 November 2013
Source:Journal of Molecular Biology</br>
Author(s): Kelly Sackett , Matthew J. Nethercott , Zhaoxiong Zheng , David P. Weliky</br>
The HIV gp41 protein catalyzes fusion between viral and target cell membranes. Although the ~20-residue N-terminal fusion peptide (FP) region is critical for fusion, the structure of this region is not...
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11-16-2013 03:14 PM
[NMR paper] Identification of fragments targeting an alternative pocket on HIV-1 gp41 by NMR screening and similarity searching.
Identification of fragments targeting an alternative pocket on HIV-1 gp41 by NMR screening and similarity searching.
Identification of fragments targeting an alternative pocket on HIV-1 gp41 by NMR screening and similarity searching.
Bioorg Med Chem Lett. 2013 Jul 22;
Authors: Chu S, Gochin M
Abstract
The HIV-1 envelope glycoprotein gp41 fusion intermediate is a promising drug target for inhibiting viral entry. However, drug development has been impeded by challenges inherent in mediating the underlying protein-protein interaction. Here...
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
J Biol Chem. 2011 Jul 8;286(27):23975-81
Authors: Celigoy J, Ramirez B, Tao L, Rong L, Yan L, Feng YR, Quinnan GV, Broder CC, Caffrey M
Abstract
The HIV envelope glycoprotein gp120 plays a critical role in virus entry, and thus, its structure is of extreme interest for the development of novel therapeutics and vaccines. To date, high resolution structural information about gp120 in complex with gp41 has proven...
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09-09-2011 06:42 PM
[NMR paper] The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics de
The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy.
Related Articles The interactions of the HIV gp41 fusion peptides with zwitterionic membrane mimics determined by NMR spectroscopy.
Biochim Biophys Acta. 2004 Nov 17;1667(1):67-81
Authors: Morris KF, Gao X, Wong TC
The wild-type (wt) N-terminal 23-residue fusion peptide (FP) of the human immunodeficiency virus (HIV) fusion protein gp41 and its V2E mutant have been studied by nuclear magnetic resonance (NMR) spectroscopy in...
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11-24-2010 10:03 PM
[NMR paper] Conformational study of fragments of envelope proteins (gp120: 254-274 and gp41: 519-
Conformational study of fragments of envelope proteins (gp120: 254-274 and gp41: 519-541) of HIV-1 by NMR and MD simulations.
Related Articles Conformational study of fragments of envelope proteins (gp120: 254-274 and gp41: 519-541) of HIV-1 by NMR and MD simulations.
J Pept Sci. 2004 Jun;10(6):363-80
Authors: Kanyalkar M, Srivastava S, Saran A, Coutinho E
The envelope proteins, gp 120 and gp41 of HIV-1, play a crucial role in receptor (CD4+ lymphocytes) binding and membrane fusion. The fragment 254-274 of gp120 is conserved in all strains of...
HIV-1 Envelope Protein gp41: An NMR Study of Dodecyl Phosphocholine Embedded gp41 Reveals a Dynamic Prefusion Intermediate Conformation.
Linear Mode
