Membrane Fusion Triggering

@article{Navaratnarajah2012MembraneFT,
  title={Membrane Fusion Triggering},
  author={C. Navaratnarajah and Surendra S. Negi and W. Braun and R. Cattaneo},
  journal={The Journal of Biological Chemistry},
  year={2012},
  volume={287},
  pages={38543 - 38551}
}
Background: The measles virus hemagglutinin stalk transmits the signal that triggers membrane fusion. Results: Functional analyses based on covalent tetramerization followed by disulfide bond reduction identify three modules in the upper half of the stalk. Conclusion: The modules have following functions (top-to-bottom): linker, spacer/signal conduction, contact with the F-trimer. Significance: Modules with similar structure and function may exist in attachment protein stalks of other… Expand
The Measles Virus Hemagglutinin Stalk: Structures and Functions of the Central Fusion Activation and Membrane-Proximal Segments
TLDR
While certain residues of the central stalk segment confer specificity to the interaction with the fusion protein trimer, others are necessary to allow folding of the H-oligomer in a standard conformation conducive to fusion triggering, and still other residues sustain the conformational change that transmits the fusion-triggering signal. Expand
Sequential Conformational Changes in the Morbillivirus Attachment Protein Initiate the Membrane Fusion Process
TLDR
This study reveals essential mechanistic requirements governing the activation of the morbillivirus membrane fusion cascade and spotlights the H-stalk “spacer” microdomain as a possible drug target for antiviral therapy. Expand
Probing the Functions of the Paramyxovirus Glycoproteins F and HN with a Panel of Synthetic Antibodies
TLDR
A model for F activation in which the attachment protein head domains move following receptor binding to expose HN stalk residues critical for triggering F is proposed, and a library of synthetic antibodies to F protein and the receptor binding protein was generated in bacteriophage to understand the steps in viral membrane fusion. Expand
A residue located at the junction of the head and stalk regions of measles virus fusion protein regulates membrane fusion by controlling conformational stability.
TLDR
Located in the HR-B domain just at the junction between the head and stalk regions, amino acid 465 is endowed with a possible ability to either destabilize or stabilize the F protein depending on its molecular volume and the direction of the side chain, regulating fusion activity of measles virus F protein. Expand
Hydrophobic and Charged Residues in the Central Segment of the Measles Virus Hemagglutinin Stalk Mediate Transmission of the Fusion-Triggering Signal
TLDR
It is documented that exact conservation of most residues in the 92 through 99 segment is essential for function, and hydrophobic and charged residues inThe 104 through 125 segment, arranged with helical periodicity, are critical for F protein interactions and signal transmission. Expand
Structure of the Parainfluenza Virus 5 (PIV5) Hemagglutinin-Neuraminidase (HN) Ectodomain
TLDR
The x-ray crystal structure of parainfluenza virus 5 (PIV5) HN ectodomain is reported in a “2-heads-up/2- heads-down” conformation which supports a model in which the heads of HN transition from down to up upon receptor binding thereby releasing steric constraints and facilitating the interaction between critical HN-stalk residues and F. Expand
Activation of paramyxovirus membrane fusion and virus entry.
TLDR
The data indicating that paramyxovirus attachment glycoproteins shield activating residues within their N-terminal stalk domains, which are then exposed upon receptor binding, leading to the activation of the fusion protein by a 'provocateur' mechanism are reviewed. Expand
Primary resistance mechanism of the canine distemper virus fusion protein against a small-molecule membrane fusion inhibitor.
TLDR
Designing 3G-resistant CDV F mutants by introducing single cysteine residues at hydrophobic core positions of the helical stalk region suggested that the fusion inhibitor 3G stabilizes prefusionCDV F trimers by docking at the top of the stalk domain. Expand
Differential Features of Fusion Activation within the Paramyxoviridae
TLDR
A better understanding of conserved and distinct features that govern the entry of protein-using versus SA-using PMVs will inform the rational design of broader spectrum therapeutics that impede this process. Expand
Role of the head-stalk linker region (aa115-122) of Newcastle disease virus haemagglutinin-neuraminidase in regulating fusion triggering.
TLDR
Analysis of mutants constructed by deleting or substituting the linker region of Newcastle disease virus haemagglutinin-neuraminidase with the corresponding sequences of other paramyxoviruses suggested that the head-stalk linker could regulate the fusion triggering at both full-length and headless HN levels. Expand
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Six residues that are required specifically for signal transmission are characterized; their mutation interferes with fusion, although still allowing efficient F-protein processing and cell surface transport, and the signal receipt mechanism may be conserved among paramyxoviruses. Expand
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