Structure and function of membrane fusion peptides

Tamm, Lukas K.; Han, Xing; Li, Yinling; Lai, Alex L.

doi:10.1002/bip.10261

Cited by 86 publications

(84 citation statements)

References 33 publications

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“…FPs are small (ϳ20 -30 residues) regions of mostly apolar residues, frequently enriched in glycine, and usually highly conserved within the fusion proteins of different strains of the same virus (21). The enveloped virus FPs are critical for fusion activity and highly sensitive to mutation, and synthetic versions of these peptides insert into lipid bilayers to promote lipid mixing (21,22).…”

Section: * This Research Was Supported In Part By a Grant From The Camentioning

confidence: 99%

Features of a Spatially Constrained Cystine Loop in the p10 FAST Protein Ectodomain Define a New Class of Viral Fusion Peptides

Barry¹,

Key²,

Haddad³

et al. 2010

Journal of Biological Chemistry

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The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral membrane fusion proteins. With ectodomains of only ϳ20 -40 residues, it is unclear how such diminutive fusion proteins can mediate cell-cell fusion and syncytium formation. Contained within the 40-residue ectodomain of the p10 FAST protein resides an 11-residue sequence of moderately apolar residues, termed the hydrophobic patch (HP). Previous studies indicate the p10 HP shares operational features with the fusion peptide motifs found within the enveloped virus membrane fusion proteins. Using biotinylation assays, we now report that two highly conserved cysteine residues flanking the p10 HP form an essential intramolecular disulfide bond to create a cystine loop. Mutagenic analyses revealed that both formation of the cystine loop and p10 membrane fusion activity are highly sensitive to changes in the size and spatial arrangement of amino acids within the loop. The p10 cystine loop may therefore function as a cystine noose, where fusion peptide activity is dependent on structural constraints within the noose that force solvent exposure of key hydrophobic residues. Moreover, inhibitors of cell surface thioreductase activity indicate that disruption of the disulfide bridge is important for p10-mediated membrane fusion. This is the first example of a viral fusion peptide composed of a small, spatially constrained cystine loop whose function is dependent on altered loop formation, and it suggests the p10 cystine loop represents a new class of viral fusion peptides.Membrane fusion is an essential process involved in an abundance of biological events, including sperm-egg fusion, multinucleated myotube formation, exocytosis, and enveloped virus entry (1). The fusion reaction is catalyzed by specialized membrane fusion proteins designed to alter bilayer structure and bring about membrane merger. The membrane fusion proteins of various enveloped viruses represent some of the best characterized examples of such fusion catalysts (2). Detailed structural and functional analysis of diverse enveloped virus membrane fusion proteins reveals a common pathway of protein-mediated membrane fusion. Triggered exposure of a hydrophobic fusion peptide (FP), 3 normally sequestered within the complex pre-fusion ectodomain structure of these proteins, results in FP insertion into the donor and/or target membranes. Subsequent structural remodeling of these large ectodomains generates a trimeric hairpin structure that draws the two membranes together, driving lipid mixing (also referred to as hemifusion) and pore formation and expansion (3, 4). Despite a wealth of information, the precise mechanisms by which FPs and conformational remodeling of enveloped virus fusion proteins mediate lipid bilayer rearrangement and fusion remain unclear.The reovirus fusion-associated small transmembrane (FAST) proteins are a singular family of viral membrane fusion proteins. Although many nonenveloped viruses encode proteins involved in membrane permeabilization (...

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Section: * This Research Was Supported In Part By a Grant From The Camentioning

confidence: 99%

Features of a Spatially Constrained Cystine Loop in the p10 FAST Protein Ectodomain Define a New Class of Viral Fusion Peptides

Barry¹,

Key²,

Haddad³

et al. 2010

Journal of Biological Chemistry

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“…However, the nature of the interaction of viral fusion proteins with membranes and the mechanism by which these proteins accelerate the formation of membrane fusion intermediates are poorly understood [8]. To simulate protein-mediated fusion, many studies on peptide-induced membrane fusion have been conducted on model membranes such as liposomes and have employed synthetic peptides corresponding to the putative fusion sequences of viral proteins [9][10][11]. On the other hand and due to the fact that membraneassociated peptides often show a remarkable structural behaviour, the conformational study of these sequences is important to get information about their activities [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Liposome destabilization induced by synthetic lipopeptides corresponding to envelope and non-structural domains of GBV-C/HGV virus. Conformational requirements for leakage

Fernández-Vidal

Rojo

Herrera

et al. 2008

Biophysical Chemistry

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Liposome destabilization induced by synthetic lipopeptides corresponding to envelope and non-structural domains of gbv-c/hgv virus. conformational requirements for leakage, Biophysical Chemistry (2007Chemistry ( ), doi: 10.1016Chemistry ( /j.bpc.2007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT LIPOSOME DESTABILIZATION INDUCED BY SYNTHETIC LIPOPEPTIDES CORRESPONDING TO ENVELOPE AND NON-STRUCTURAL DOMAINS OF GBV-C/HGV VIRUS. CONFORMATIONAL REQUIREMENTS FOR LEAKAGE A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 2 AbstractLiposomes have been used primarily as a model system for studying biological membranes.

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“…The presence of a fusion peptide is thus a feature of both Class I and II viral fusion proteins (21)(22)(23); these hydrophobic sequences are involved in driving the initial partitioning of the fusion protein into the target membrane, making the viral envelope glycoprotein an integral component of both viral and cellular membranes. The real interplay between fusion peptides and the membrane is still unknown.…”

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confidence: 99%

Fusogenic Domains in Herpes Simplex Virus Type 1 Glycoprotein H

Galdiero

Falanga²,

Vitiello

et al. 2005

Journal of Biological Chemistry

172

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Infection of eukaryotic cells by enveloped viruses requires fusion between the viral envelope and the cellular plasma or endosomal membrane. The actual merging of the two membranes is mediated by viral envelope glycoproteins, which generally contain a highly hydrophobic region termed the fusion peptide. The entry of herpesviruses is mediated by three conserved proteins: glycoproteins B, H (gH), and L. However, how fusion is executed remains unknown. Herpes simplex virus type 1 gH exhibits features typical of viral fusion glycoproteins, and its ectodomain seems to contain a putative internal fusion peptide. Here, we have identified additional internal segments able to interact with membranes and to induce membrane fusion of large unilamellar vesicles. We have applied the hydrophobicity-atinterface scale proposed by Wimley and White (Wimley, W. C., and White, S. H. (1996) Nat. Struct. Biol. 3, 842-848) to identify six hydrophobic stretches within gH with a tendency to partition into the membrane interface, and four of them were able to induce membrane fusion. Experiments in which equimolar mixtures of gH peptides were used indicated that different fusogenic regions may act in a synergistic way. The functional and structural characterization of these segments suggests that herpes simplex virus type 1 gH possesses several fusogenic internal peptides that could participate in the actual fusion event.

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Structure and function of membrane fusion peptides

Cited by 86 publications

References 33 publications

Features of a Spatially Constrained Cystine Loop in the p10 FAST Protein Ectodomain Define a New Class of Viral Fusion Peptides

Features of a Spatially Constrained Cystine Loop in the p10 FAST Protein Ectodomain Define a New Class of Viral Fusion Peptides

Liposome destabilization induced by synthetic lipopeptides corresponding to envelope and non-structural domains of GBV-C/HGV virus. Conformational requirements for leakage

Fusogenic Domains in Herpes Simplex Virus Type 1 Glycoprotein H

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