title: HIV-1 envelope protein gp41: an NMR study of dodecyl phosphocholine embedded gp41 reveals a dynamic prefusion intermediate conformation.
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 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.
authors.affiliation: Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892-0520, USA. Electronic address: nall@nmr.mpibpc.mpg.de.
authors.forename: Nils-Alexander
authors.initials: NA
authors.lastname: Lakomek
authors.affiliation: Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, MD 20892-2775, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Kaufman
authors.affiliation: Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, MD 20892-2775, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Stahl
authors.affiliation: Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, MD 20892-2775, USA. Electronic address: wingfiep@mail.nih.gov.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wingfield
mesh_terms: D003902:Detergents / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry; D008823:Micelles; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D053586:Virus Internalization
chemical_list: D003902:Detergents; D015700:HIV Envelope Protein gp41; D008823:Micelles; C514787:gp41 protein, Human immunodeficiency virus 1; D010767:Phosphorylcholine; C028810:dodecylphosphocholine