The HIV Fusion Peptide Adopts Intermolecular Parallel β-Sheet Structure in Membranes when Stabilized by the Adjacent N-Terminal Heptad Repeat: A 13C FTIR Study

Sackett, Kelly; Shai, Yechiel

doi:10.1016/j.jmb.2005.05.030

Cited by 46 publications

(70 citation statements)

References 87 publications

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“…However, IR data on constructs which contain the first 34 or 70 residues of gp41 support an in-register parallel strand arrangement (44). These latter constructs contain the 23-residues of HFPmn as well as an additional 11 or 47 C-terminal residues.…”

Section: Strand Arrangementmentioning

confidence: 92%

“…Models for the helical structure have been developed based on nuclear magnetic resonance (NMR), electron spin resonance (ESR), infrared (IR), and circular dichroism (CD) data, as well as computer simulations (33)(34)(35)(36)(37)(38)(39). A β hairpin model for non-helical structure has been proposed based on IR and surface activity measurements in membranes (40).Fluorescence, ESR, IR, and solid-state NMR data also suggest that the nonhelical HFPs in membranes form oligomeric structures (10,(41)(42)(43)(44). These oligomeric structures may be important as evidenced by envelope protein trimerization and by experiments and modeling which indicate that the fusion site contains multiple trimers and a corresponding high HFP concentration (17,18,45).…”

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confidence: 99%

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Conformational Flexibility and Strand Arrangements of the Membrane-Associated HIV Fusion Peptide Trimer Probed by Solid-State NMR Spectroscopy

et al. 2006

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The human immunodeficiency virus (HIV) fusion peptide (HFP) is the N-terminal apolar region of the HIV gp41 fusion protein and interacts with target cell membranes and promotes membrane fusion. The free peptide catalyzes vesicle fusion at least to the lipid mixing stage and serves as a useful model fusion system. For gp41 constructs which lack the HFP, high-resolution structures show trimeric protein and suggest that at least three HFPs interact with the membrane with their C-termini in close proximity. In addition, previous studies have demonstrated that HFPs which are cross-linked at their C-termini to form trimers (HFPtr) catalyze fusion at a rate which is 15−40 times greater than noncross-linked HFP. In the present study, the structure of membrane-associated HFPtr was probed with solid-state nuclear magnetic resonance (NMR) methods. Chemical shift and intramolecular 13 CO-15 N distance measurements show that the conformation of the Leu-7 to Phe-11 region of HFPtr has predominant helical conformation in membranes without cholesterol and β strand conformation in membranes containing ∼30 mol% cholesterol. Interstrand 13 CO-13 CO and 13 CO-15 N distance measurements were not consistent with an in-register parallel strand arrangement but were consistent with either: (1) parallel arrangement with adjacent strands tworesidues out-of-register; or (2) antiparallel arrangement with adjacent strand crossing between Phe-8 and Leu-9. Arrangement (1) could support the rapid fusion rate of HFPtr because of placement of the apolar N-terminal regions of all strands on the same side of the oligomer while arrangement (2) could support the assembly of multiple fusion protein trimers. KeywordsHIV; fusion peptide; cholesterol; membranes; NMR; trimer Enveloped viruses such as human immunodeficiency virus (HIV) are surrounded by a membrane and infect cells through fusion between the viral membrane and the target cell membrane (1,2). This process is mediated by envelope proteins which traverse the viral membrane (3). For HIV, the gp41 envelope protein has a ∼170-residue ectodomain region † This work was supported by NIH award AI47153 to D. P. W. * To whom correspondence should be addressed. Telephone: 517−355−9715. Fax: 517−353−1793. Email: weliky@chemistry.msu.edu.. SUPPORTING INFORMATION AVAILABLE Equations are derived for determination of (ΔS/S 0 ) cor for REDOR and fpCTDQBU analyses. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2008 October 20. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript which lies outside the viral membrane and contains a N-terminal ∼20-residue apolar "fusion peptide" (HFP). The HFP interacts with the target cell membrane and plays an essential role in membrane fusion (4). Peptides composed of the HFP sequence induce fusion between large unilamellar vesicles (LUVs) and between erythrocytes (5,6). There are similar mutation/fusion activity relationships...

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Section: Strand Arrangementmentioning

confidence: 92%

mentioning

confidence: 99%

Conformational Flexibility and Strand Arrangements of the Membrane-Associated HIV Fusion Peptide Trimer Probed by Solid-State NMR Spectroscopy

et al. 2006

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“…So far, structural information for many fusion peptides has been revealed by a variety of spectroscopic and computational methods. The HIV gp41 fusion peptide was shown to form an ␣-helix in membrane-mimicking environments (23,30,42). The three-dimensional structure of the Ebola fusion peptide displays a 3 10 -helix in the central part of the molecule (13).…”

Section: Discussionmentioning

confidence: 99%

“…The three-dimensional structure of the fusion peptide is essential to understanding this mechanism. Some of the structures of fusion peptides of different viruses, such as the fusion peptide of influenza virus hemagglutinin (HA) (16,28) and the fusion peptide of HIV gp41 (7,23,30,42), have been determined by nuclear magnetic resonance (NMR) and other techniques.…”

mentioning

confidence: 99%

Mutagenesis and Nuclear Magnetic Resonance Analyses of the Fusion Peptide of Helicoverpa armigera Single Nucleocapsid Nucleopolyhedrovirus F Protein

Tan

Jiang

Yin

et al. 2008

J Virol

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“…As it has been proposed for the HIV fusion peptide, hydrophobic monomers of H5WYG could self-assemble into a parallel β-sheet configuration. [19] Indeed, there are possibilities for inter-peptide π -stacking of aromatic side-chains of the two phenylalanines in positions 3 and 10 as well as of the two tryptophans in positions 14 and 21. Moreover, uncharged imidazole groups of histidine residues in positions 4, 8, 11, 15 and 19 can also form π -stacking.…”

Section: H15amentioning

confidence: 99%

Involvement of histidines 11, 15 and 19 in the binding of zinc to the fusogenic H5WYG peptide

2009

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The histidine-rich GLFHAIAHFIHGGWHGLIHGWYG peptide (H5WYG) coordinates a Zn2+ ion and forms a stable peptide-metal complex promoting membrane fusion at physiologic pH. In our previous article titled 'Histidine-rich peptide: evidence for a single zinc-binding site on H5WYG peptide that promotes membrane fusion at neutral pH' in Journal of Mass Spectrometry (2009, 44, 81-89), tandem mass spectrometry experiments have provided evidence for the binding of a single Zn2+ ion to H5WYG and suggested that this binding is shared between H11, H19 and probably H15 residues. To clarify the involvement of these histidine residues in the binding to the Zn2+ ion and especially to remove the doubt about the implication of the H15 residue, here we have used three H5WYG mutants termed H5WYGH11A, H5WYGH15A and H5WYGH19A, whose H11, H15 and H19 residues were replaced with an alanine residue. The novelty introduced by these new tandem mass spectrometry experiments performed with the mutants is the demonstration that H15 is involved in the binding of the single Zn2+ ion and that it may even favour the setting of another Zn2+ ion. Thus, the three histidines H11, H15 and H19 could lead to a specific structuring of H5WYG that can promote membrane fusion upon the binding of zinc.

show abstract

The HIV Fusion Peptide Adopts Intermolecular Parallel β-Sheet Structure in Membranes when Stabilized by the Adjacent N-Terminal Heptad Repeat: A 13C FTIR Study

Cited by 46 publications

References 87 publications

Conformational Flexibility and Strand Arrangements of the Membrane-Associated HIV Fusion Peptide Trimer Probed by Solid-State NMR Spectroscopy

Conformational Flexibility and Strand Arrangements of the Membrane-Associated HIV Fusion Peptide Trimer Probed by Solid-State NMR Spectroscopy

Mutagenesis and Nuclear Magnetic Resonance Analyses of the Fusion Peptide of Helicoverpa armigera Single Nucleocapsid Nucleopolyhedrovirus F Protein

Involvement of histidines 11, 15 and 19 in the binding of zinc to the fusogenic H5WYG peptide

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