Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission

Lorizate, Maier; Huarte, Nerea; Sáez‐Cirión, Asier; Nieva, José L.

doi:10.1016/j.bbamem.2007.12.018

Cited by 64 publications

(92 citation statements)

References 133 publications

(232 reference statements)

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“…This longer membrane-suitable region is observed for the PIV5 C-term-TM and contributes to fusion (57). It is also observed in other viruses such as influenza (51) and HIV, where shortening the length of C-term-TM helices can halt the fusion process (79,80). Fig.…”

Section: Discussionmentioning

confidence: 78%

Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion

Donald¹,

Zhang

Fiorin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Membrane fusion is required for diverse biological functions ranging from viral infection to neurotransmitter release. Fusogenic proteins increase the intrinsically slow rate of fusion by coupling energetically downhill conformational changes of the protein to kinetically unfavorable fusion of the membrane-phospholipid bilayers. Class I viral fusogenic proteins have an N-terminal hydrophobic fusion peptide (FP) domain, important for interaction with the target membrane, plus a C-terminal transmembrane (C-term-TM) helical membrane anchor. The role of the water-soluble regions of fusogenic proteins has been extensively studied, but the contributions of the membrane-interacting FP and C-term-TM peptides are less well characterized. Typically, FPs are thought to bind to membranes at an angle that allows helix penetration but not traversal of the lipid bilayer. Here, we show that the FP from the paramyxovirus parainfluenza virus 5 fusogenic protein, F, forms an N-terminal TM helix, which self-associates into a hexameric bundle. This FP also interacts strongly with the C-term-TM helix. Thus, the fusogenic F protein resembles SNARE proteins involved in vesicle fusion by having water-soluble coiled coils that zipper during fusion and TM helices in both membranes. By analogy to mechanosensitive channels, the force associated with zippering of the water-soluble coiled-coil domain is expected to lead to tilting of the FP helices, promoting interaction with the C-term-TM helices. The energetically unfavorable dehydration of lipid headgroups of opposing bilayers is compensated by thermodynamically favorable interactions between the FP and C-term-TM helices as the coiled coils zipper into the membrane phase, leading to a pore lined by both lipid and protein.T he basic mechanisms of viral membrane fusion have been studied extensively, but major gaps remain in our understanding of the relative roles of lipidic intermediates and viral fusogenic proteins in lowering the energy barrier for the overall process (1-4). The most common mechanistic hypothesis concerning enveloped viral fusion is that fusogenic proteins primarily serve to bring the target cell and viral membranes into proximity. Fusion occurs in a multistep process, in which the virus first binds to a specific receptor; this event and/or other environmental cues then cause a conformational change in the protein, leading to a metastable state with an exposed hydrophobic fusion peptide (FP) that binds to the target membrane. Once engaged with the bilayer, a second energetically favorable conformational change in the fusogenic protein then exerts a force pulling the FP toward the viral membrane, in effect reeling the host and viral membranes together.The conformational changes involved in the water-soluble portions of viral fusogenic proteins have been largely elucidated, but the roles of the membrane-binding FP and the C-terminal transmembrane (C-term-TM) anchor are less clear. After the crystal structure of the prefusogenic form of influenza hemagglutinin (HA) was solved...

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Section: Discussionmentioning

confidence: 78%

Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion

Donald¹,

Zhang

Fiorin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This implies that peptides recreating its native structure might in principle compose stand-alone HIV vaccines (6,13,19,20,72,73). Although intensively studied, data supporting the structural MPER connectivity within a synthetic peptide vaccine were lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Given its proximity to the envelope surface and the unusual concentration of aromatic residues, it has been proposed that structuring coupled to membrane partitioning may play a crucial role in determining the structure and orientation of MPER epitopes, which in turn will have an impact on immunogenicity (19,62,72,83). Thus, we studied in parallel the MPERp structure and immunogenicity in two different liposomal formulations (Figs.…”

Section: Figure 8 Recovered Responses After Vaccination With the Popmentioning

confidence: 99%

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Serrano

Araujo

Apellániz

et al. 2014

Journal of Biological Chemistry

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Background: HIV-1 vaccines should elicit broadly neutralizing antibodies as the gp41 "membrane-proximal external region" targeting MAb2F5. Results: NMR disclosed unprecedented 2F5 peptide-epitope structures. Although overall conformation was preserved in different adjuvants, recovered antibodies after vaccination were functionally different. Conclusion: Membrane-inserted helical oligomers may encompass effective 2F5 peptide vaccines. Significance: Disclosing the structures that generate 2F5-like antibodies may guide future vaccine development.

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“…[26][27][28][29][30] Liposomes have been successfully used in the delivery of bioactive proteins into flagellated E. coli envelope, 31 and to transfect competent E. coli and Mycoplasma capricolum cells with encapsulated plasmid DNA. 32,33 By using liposomes made of lipid extracts from the whole bacterial membranes of Salmonella minnesota RE595 (the composition and lipids were not identified), Tomlinson et al 33 successfully incorporated phospholipid and proteins into gram-negative bacteria and confirmed that a fusion process was involved in this extensive phospholipid transfer.…”

Section: Discussionmentioning

confidence: 99%

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Wang¹,

Ma²,

Khalil³

et al. 2016

IJN

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Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. Methods In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipa lmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol) in a fluid state, and intact bacterial cells, by lipid mixing assay. Results The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66%) or P. aeruginosa (44%) seems to be correlated to their outer membrane phosphatidylethanolamine (PE) phospholipids composition (91% and 71%, respectively). Divalent cations increased the degree of fusion in the sequence Fe 2+ > Mg 2+ > Ca 2+ > Ba 2+ whereas temperatures lower than the phase transition temperature of DPPC/DMPG (9:1) vesicles decreased their fusion capacity. Acidic as well as basic pHs conferred higher degrees of fusion (54% and 45%, respectively) when compared to neutral pH (35%). Conclusion Based on the results of this study, a possible mechanism involving cationic bridging between bacterial negatively charged lipopolysaccharide and fluid liposomes DMPG phospholipids was outlined. Furthermore, the fluid liposomal-encapsulated tobramycin was prepared, and the in vitro bactericidal effects were also investigated.

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Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission

Cited by 64 publications

References 133 publications

Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion

Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

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