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

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.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0023-E489-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-5BC7-4
Genre: Journal Article

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 Creators:
Lakomek, N. A.1, Author              
Kaufman, J. D., Author
Stahl, S. J., Author
Wingfield, P. T., Author
Affiliations:
1Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              

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 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.

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Language(s): eng - English
 Dates: 2014-09-02
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.str.2014.06.016
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Title: Structure
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 22 (9) Sequence Number: - Start / End Page: 1311 - 1321 Identifier: -