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Journal Article

HIV-1 envelope protein gp41: An NMR study of dodecyl phosphocholine embedded gp41 reveals a dynamic prefusion intermediate conformation.

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Lakomek,  N. A.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

2059297.pdf
(Publisher version), 3MB

Supplementary Material (public)

2059297_Suppl_1.pdf
(Supplementary material), 687KB

2059297_Suppl_2.xls
(Supplementary material), 37KB

2059297_Suppl_3.xls
(Supplementary material), 50KB

2059297_Suppl_4.pdf
(Supplementary material), 3MB

Citation

Lakomek, N. A., Kaufman, J. D., Stahl, S. J., & Wingfield, P. T. (2014). HIV-1 envelope protein gp41: An NMR study of dodecyl phosphocholine embedded gp41 reveals a dynamic prefusion intermediate conformation. Structure, 22(9), 1311-1321. doi:10.1016/j.str.2014.06.016.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0023-E489-E
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 gp4127–194, comprising the transmembrane region and reconstituted in dodecyl phosphocholine (DPC) micelles. The protein is mainly α-helical, but experiences internal dynamics on the nanosecond and micro to millisecond time scale and transient α-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.