Viral Fusion Peptides: A Tool Set to Disrupt and Connect Biological Membranes

2000 ◽  
Vol 20 (6) ◽  
pp. 501-518 ◽  
Author(s):  
Lukas K. Tamm ◽  
Xing Han
Keyword(s):  
Lipid Bilayers ◽  
Biological Membrane ◽  
Membrane Curvature ◽  
Current Evidence ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Membrane Surfaces ◽  
Self Association ◽  
Α Helix ◽  
And Function

The structure and function of viral fusion peptides are reviewed. The fusion peptides of influenza virus hemagglutinin and human immunodeficiency virus are used as paradigms. Fusion peptides associated with lipid bilayers are conformationally polymorphic. Current evidence suggests that the fusion-promoting state is the obliquely inserted α-helix. Fusion peptides also have a tendency to self-associate into γ-sheets at membrane surfaces. Although the conformational conversion between α- and γ-states is reversible under controlled conditions, its physiological relevance is not yet known. The energetics of peptide insertion and self-association could be measured recently using more soluble “second generation” fusion peptides. Fusion peptides have been reported to change membrane curvature and the state of hydration of membrane surfaces. The combined results are built into a model for the mechanism by which fusion peptides are proposed to assist in biological membrane fusion.

scholarly journals Identification and Characteristics of Fusion Peptides Derived From Enveloped Viruses

2021 ◽  
Vol 9 ◽  
Author(s):  
Camille Lozada ◽  
Thomas M. A. Barlow ◽  
Simon Gonzalez ◽  
Nadège Lubin-Germain ◽  
Steven Ballet
Keyword(s):  
Fusion Proteins ◽  
Current Evidence ◽  
Common Mechanism ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Enveloped Viruses ◽  
Viral Glycoproteins ◽  
Viral Fusion Proteins ◽  
Different Characteristics

Membrane fusion events allow enveloped viruses to enter and infect cells. The study of these processes has led to the identification of a number of proteins that mediate this process. These proteins are classified according to their structure, which vary according to the viral genealogy. To date, three classes of fusion proteins have been defined, but current evidence points to the existence of additional classes. Despite their structural differences, viral fusion processes follow a common mechanism through which they exert their actions. Additional studies of the viral fusion proteins have demonstrated the key role of specific proteinogenic subsequences within these proteins, termed fusion peptides. Such peptides are able to interact and insert into membranes for which they hold interest from a pharmacological or therapeutic viewpoint. Here, the different characteristics of fusion peptides derived from viral fusion proteins are described. These criteria are useful to identify new fusion peptides. Moreover, this review describes the requirements of synthetic fusion peptides derived from fusion proteins to induce fusion by themselves. Several sequences of the viral glycoproteins E1 and E2 of HCV were, for example, identified to be able to induce fusion, which are reviewed here.

Arfs and membrane lipids: sensing, generating and responding to membrane curvature

2008 ◽  
Vol 414 (2) ◽  
pp. e1-e2 ◽  
Author(s):  
Julie G. Donaldson
Keyword(s):  
Membrane Trafficking ◽  
Membrane Lipids ◽  
Membrane Curvature ◽  
Coat Proteins ◽  
Membrane Interaction ◽  
Protein Activation ◽  
Membrane Surfaces ◽  
Transport Vesicles ◽  
Biochemical Journal ◽  
Α Helix

Arf family GTP-binding proteins function in the regulation of membrane-trafficking events and in the maintenance of organelle structure. They act at membrane surfaces to modify lipid composition and to recruit coat proteins for the generation of transport vesicles. Arfs associate with membranes through insertion of an N-terminal myristoyl moiety in conjunction with an adjacent amphipathic α-helix, which embeds in the lipid bilayer when Arf1 is GTP-bound. In this issue of the Biochemical Journal, Lundmark et al. report that myristoylated Arfs in the presence of GTP bind to and cause tubulation of liposomes, and that GTP exchange on to Arfs is more efficient in the presence of liposomes of smaller diameter (increased curvature). These findings suggest that Arf protein activation and membrane interaction may initiate membrane curvature that will be enhanced further by coat proteins during vesicle formation.

scholarly journals The Central Proline of an Internal Viral Fusion Peptide Serves Two Important Roles

2000 ◽  
Vol 74 (4) ◽  
pp. 1686-1693 ◽  
Author(s):  
S. E. Delos ◽  
J. M. Gilbert ◽  
J. M. White
Keyword(s):  
Leukemia Virus ◽  
Fusion Peptide ◽  
Viral Fusion ◽  
Fusion Peptides ◽  
Loop Order ◽  
Hydrophobic Residues ◽  
Reverse Turn ◽  
Α Helix ◽  
Avian Sarcoma ◽  
Β Sheet

ABSTRACT The fusion peptide of the avian sarcoma/leukosis virus (ASLV) envelope protein (Env) is internal, near the N terminus of its transmembrane (TM) subunit. As for most internal viral fusion peptides, there is a proline near the center of this sequence. Robson-Garnier structure predictions of the ASLV fusion peptide and immediate surrounding sequences indicate a region of order (β-sheet), a tight reverse turn containing the proline, and a second region of order (α-helix). Similar motifs (order, turn or loop, order) are predicted for other internal fusion peptides. In this study, we made and analyzed 12 Env proteins with substitutions for the central proline of the fusion peptide. Env proteins were expressed in 293T cells and in murine leukemia virus pseudotyped virions. We found the following. (i) All mutant Envs form trimers, but when the bulky hydrophobic residues phenylalanine or leucine are substituted for proline, trimerization is weakened. (ii) Surprisingly, the proline is required for maximal processing of the Env precursor into its surface and TM subunits; the amount of processing correlates linearly with the propensity of the substituted residue to be found in a reverse turn. (iii) Nonetheless, proteolytically processed forms of all Envs are preferentially incorporated into pseudotyped virions. (iv) All Envs bind receptor with affinity greater than or equal to wild-type affinity. (v) Residues that support high infectivity cluster with proline at intermediate hydrophobicity. Infectivity is not supported by mutant Envs in which charged residues are substituted for proline, nor is it supported by the trimerization-defective phenylalanine and leucine mutants. Our findings suggest that the central proline in the ASLV fusion peptide is important for the formation of the native (metastable) Env structure as well as for membrane interactions that lead to fusion.

scholarly journals Secretory and viral fusion may share mechanistic events with fusion between curved lipid bilayers

1998 ◽  
Vol 95 (16) ◽  
pp. 9274-9279 ◽  
Author(s):  
JinKeun Lee ◽  
Barry R. Lentz
Keyword(s):  
Membrane Fusion ◽  
Lipid Bilayers ◽  
Biological Membrane ◽  
Activation Energies ◽  
Membrane Lipid ◽  
Striking Similarity ◽  
Fusion Pore ◽  
Viral Fusion ◽  
Lipid Molecule ◽  
Free Model

Activation energies for the individual steps of secretory and viral fusion are reported to be large [Oberhauser, A. F., Monck, J. R. & Fernandez, J. M. (1992) Biophys. J. 61, 800–809; Clague, M. J., Schoch, C., Zech, L. & Blumenthal, R. (1990) Biochemistry 29, 1303–1308]. Understanding the cause for these large activation energies is crucial to defining the mechanisms of these two types of biological membrane fusion. We showed recently that the fusion of protein-free model lipid bilayers mimics the sequence of steps observed during secretory and viral fusion, suggesting that these processes may involve common lipid, rather than protein, rearrangements. To test for this possibility, we determined the activation energies for the three steps that we were able to distinguish as contributing to the fusion of protein-free model lipid bilayers. Activation energies for lipid rearrangements associated with formation of the reversible first intermediate, with conversion of this to a semi-stable second intermediate, and with irreversible fusion pore formation were 37 kcal/mol, 27 kcal/mol, and 22 kcal/mol, respectively. The first and last of these were comparable to the activation energies observed for membrane lipid exchange (42 kcal/mol) during viral fusion and for the rate of fusion pore opening during secretory granule release (23 kcal/mol). This striking similarity suggests strongly that the basic molecular processes involved in secretory and viral fusion involve a set of lipid molecule rearrangements that also are involved in model membrane fusion.

scholarly journals Cardiolipin-Containing Lipid Membranes Attract the Bacterial Cell Division Protein DivIVA

2021 ◽  
Vol 22 (15) ◽  
pp. 8350
Author(s):  
Naďa Labajová ◽  
Natalia Baranova ◽  
Miroslav Jurásek ◽  
Robert Vácha ◽  
Martin Loose ◽  
...  
Keyword(s):  
Cell Division ◽  
Lipid Bilayers ◽  
Bacterial Cell ◽  
Lipid Membranes ◽  
Model Organism ◽  
Active Role ◽  
Membrane Curvature ◽  
Bacterial Cell Division ◽  
Division Site ◽  
Clostridioides Difficile

DivIVA is a protein initially identified as a spatial regulator of cell division in the model organism Bacillus subtilis, but its homologues are present in many other Gram-positive bacteria, including Clostridia species. Besides its role as topological regulator of the Min system during bacterial cell division, DivIVA is involved in chromosome segregation during sporulation, genetic competence, and cell wall synthesis. DivIVA localizes to regions of high membrane curvature, such as the cell poles and cell division site, where it recruits distinct binding partners. Previously, it was suggested that negative curvature sensing is the main mechanism by which DivIVA binds to these specific regions. Here, we show that Clostridioides difficile DivIVA binds preferably to membranes containing negatively charged phospholipids, especially cardiolipin. Strikingly, we observed that upon binding, DivIVA modifies the lipid distribution and induces changes to lipid bilayers containing cardiolipin. Our observations indicate that DivIVA might play a more complex and so far unknown active role during the formation of the cell division septal membrane.

scholarly journals Fracture faces of frozen membranes: 50th anniversary

2016 ◽  
Vol 27 (3) ◽  
pp. 421-423
Author(s):  
Daniel Branton
Keyword(s):  
Electron Microscopy ◽  
Lipid Bilayers ◽  
Fracture Process ◽  
Relative Proportion ◽  
50Th Anniversary ◽  
Biological Membranes ◽  
Bilayer Membrane ◽  
Biological Cells ◽  
Membrane Surfaces ◽  
Freeze Etching

In 1961, the development of an improved freeze-etching (FE) procedure to prepare rapidly frozen biological cells or tissues for electron microscopy raised two important questions. How does a frozen cell membrane fracture? What do the extensive face views of the cell’s membranes exposed by the fracture process of FE tell us about the overall structure of biological membranes? I discovered that all frozen membranes tend to split along weakly bonded lipid bilayers. Consequently, the fracture process exposes internal membrane faces rather than either of the membrane’s two external surfaces. During etching, when ice is allowed to sublime after fracturing, limited regions of the actual membrane surfaces are revealed. Examination of the fractured faces and etched surfaces provided strong evidence that biological membranes are organized as lipid bilayers with some proteins on the surface and other proteins extending through the bilayer. Membrane splitting made it possible for electron microscopy to show the relative proportion of a membrane’s area that exists in either of these two organizational modes.

scholarly journals The Many Faces of Amphipathic Helices

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 45 ◽  
Author(s):  
Manuel Giménez-Andrés ◽  
Alenka Čopič ◽  
Bruno Antonny
Keyword(s):  
Lipid Bilayers ◽  
General Scheme ◽  
Membrane Curvature ◽  
Hydrophobic Residues ◽  
Cellular Processes ◽  
Amphipathic Helices ◽  
Polar Residues ◽  
Secondary Feature ◽  
Helical Turn ◽  
The Many

Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid surfaces of cellular organelles. Using various examples, we discuss here how variations within this general scheme impart membrane-interacting AHs with different interfacial properties. Among the key parameters are: (i) the size of hydrophobic residues and their density per helical turn; (ii) the nature, the charge, and the distribution of polar residues; and (iii) the length of the AH. Depending on how these parameters are tuned, AHs can deform lipid bilayers, sense membrane curvature, recognize specific lipids, coat lipid droplets, or protect membranes from stress. Via these diverse mechanisms, AHs play important roles in many cellular processes.

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

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