1. HIV-1 Envelope Protein gp41: An NMR Study of Dodecyl Phosphocholine Embedded gp41 Reveals a Dynamic Prefusion Intermediate Conformation.
- Author
-
Lakomek, Nils-Alexander, Kaufman, Joshua D., Stahl, Stephen J., and Wingfield, Paul T.
- Subjects
- *
HIV , *NUCLEAR magnetic resonance , *DODECYL phosphocholine , *CHIMERIC proteins , *VIRAL envelope proteins , *GLYCOPROTEINS - Abstract
Summary 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 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF