scholarly journals Protonation of Individual Histidine Residues Is Not Required for the pH-Dependent Entry of West Nile Virus: Evaluation of the “Histidine Switch” Hypothesis

2009 ◽  
Vol 83 (23) ◽  
pp. 12631-12635 ◽  
Author(s):  
Steevenson Nelson ◽  
Subhajit Poddar ◽  
Tsai-Yu Lin ◽  
Theodore C. Pierson
Keyword(s):  
Life Cycle ◽  
West Nile Virus ◽  
Fusion Proteins ◽  
Viral Fusion ◽  
Ph Sensing ◽  
West Nile ◽  
Histidine Residues ◽  
E Protein ◽  
Viral Fusion Proteins ◽  
Ph Dependent

ABSTRACT Histidine residues have been hypothesized to function as sensors of environmental pH that can trigger the activity of viral fusion proteins. We investigated a requirement for histidine residues in the envelope (E) protein of West Nile virus during pH-dependent entry into cells. Each histidine was individually replaced with a nonionizable amino acid and tested functionally. In each instance, mutants capable of orchestrating pH-dependent infection were identified. These results do not support a requirement for any single histidine as a pH-sensing “switch,” and they suggest that additional features of the E protein are involved in triggering pH-dependent steps in the flavivirus life cycle.

scholarly journals Role of Electrostatic Repulsion in Controlling pH-Dependent Conformational Changes of Viral Fusion Proteins

Structure ◽  
2013 ◽  
Vol 21 (7) ◽  
pp. 1085-1096 ◽  
Author(s):  
Joseph S. Harrison ◽  
Chelsea D. Higgins ◽  
Matthew J. O’Meara ◽  
Jayne F. Koellhoffer ◽  
Brian A. Kuhlman ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Fusion Proteins ◽  
Electrostatic Repulsion ◽  
Viral Fusion ◽  
Viral Fusion Proteins ◽  
Ph Dependent

Histidine protonation and the activation of viral fusion proteins

2008 ◽  
Vol 36 (1) ◽  
pp. 43-45 ◽  
Author(s):  
Daniela S. Mueller ◽  
Thorsten Kampmann ◽  
Ragothaman Yennamalli ◽  
Paul R. Young ◽  
Bostjan Kobe ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Envelope Protein ◽  
Fusion Proteins ◽  
Side Chain ◽  
Viral Fusion ◽  
Histidine Residues ◽  
Local Environments ◽  
Viral Fusion Proteins ◽  
Dynamics Simulations

Many viral fusion proteins only become activated under mildly acidic condition (pH 4.5–6.5) close to the pKa of histidine side-chain protonation. Analysis of the sequences and structures of influenza HA (haemagglutinin) and flaviviral envelope glycoproteins has led to the identification of a number of histidine residues that are not only fully conserved themselves but have local environments that are also highly conserved [Kampmann, Mueller, Mark, Young and Kobe (2006) Structure 14, 1481–1487]. Here, we summarize studies aimed at determining the role, if any, that protonation of these potential switch histidine residues plays in the low-pH-dependent conformational changes associated with fusion activation of a flaviviral envelope protein. Specifically, we report on MD (Molecular Dynamics) simulations of the DEN2 (dengue virus type 2) envelope protein ectodomain sE (soluble E) performed under varied pH conditions designed to test the histidine switch hypothesis of Kampmann et al. (2006).

scholarly journals Mechanism of membrane fusion induced by vesicular stomatitis virus G protein

2016 ◽  
Vol 114 (1) ◽  
pp. E28-E36 ◽  
Author(s):  
Irene S. Kim ◽  
Simon Jenni ◽  
Megan L. Stanifer ◽  
Eatai Roth ◽  
Sean P. J. Whelan ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
G Protein ◽  
Vesicular Stomatitis Virus ◽  
Fusion Proteins ◽  
Low Ph ◽  
Viral Fusion ◽  
Protein Fusion ◽  
West Nile ◽  
Vesicular Stomatitis ◽  
Viral Fusion Proteins

The glycoproteins (G proteins) of vesicular stomatitis virus (VSV) and related rhabdoviruses (e.g., rabies virus) mediate both cell attachment and membrane fusion. The reversibility of their fusogenic conformational transitions differentiates them from many other low-pH-induced viral fusion proteins. We report single-virion fusion experiments, using methods developed in previous publications to probe fusion of influenza and West Nile viruses. We show that a three-stage model fits VSV single-particle fusion kinetics: (i) reversible, pH-dependent, G-protein conformational change from the known prefusion conformation to an extended, monomeric intermediate; (ii) reversible trimerization and clustering of the G-protein fusion loops, leading to an extended intermediate that inserts the fusion loops into the target-cell membrane; and (iii) folding back of a cluster of extended trimers into their postfusion conformations, bringing together the viral and cellular membranes. From simulations of the kinetic data, we conclude that the critical number of G-protein trimers required to overcome membrane resistance is 3 to 5, within a contact zone between the virus and the target membrane of 30 to 50 trimers. This sequence of conformational events is similar to those shown to describe fusion by influenza virus hemagglutinin (a “class I” fusogen) and West Nile virus envelope protein (“class II”). Our study of VSV now extends this description to “class III” viral fusion proteins, showing that reversibility of the low-pH-induced transition and architectural differences in the fusion proteins themselves do not change the basic mechanism by which they catalyze membrane fusion.

Structural comparison of three viral “fusion” proteins

1991 ◽  
Vol 19 (3) ◽  
pp. 312S-312S
Author(s):  
BRUCE H NICHOLSON ◽  
MAHMOUD NAASE
Keyword(s):  
Fusion Proteins ◽  
Viral Fusion ◽  
Structural Comparison ◽  
Viral Fusion Proteins

scholarly journals New Biophysical Approaches Reveal the Dynamics and Mechanics of Type I Viral Fusion Machinery and Their Interplay with Membranes

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 413 ◽  
Author(s):  
Mark A. Benhaim ◽  
Kelly K. Lee
Keyword(s):  
Membrane Fusion ◽  
Conformational Changes ◽  
Viral Entry ◽  
Fusion Proteins ◽  
Structural Changes ◽  
Fusion Reaction ◽  
Type I ◽  
Viral Fusion ◽  
Technological Advances ◽  
Viral Fusion Proteins

Protein-mediated membrane fusion is a highly regulated biological process essential for cellular and organismal functions and infection by enveloped viruses. During viral entry the membrane fusion reaction is catalyzed by specialized protein machinery on the viral surface. These viral fusion proteins undergo a series of dramatic structural changes during membrane fusion where they engage, remodel, and ultimately fuse with the host membrane. The structural and dynamic nature of these conformational changes and their impact on the membranes have long-eluded characterization. Recent advances in structural and biophysical methodologies have enabled researchers to directly observe viral fusion proteins as they carry out their functions during membrane fusion. Here we review the structure and function of type I viral fusion proteins and mechanisms of protein-mediated membrane fusion. We highlight how recent technological advances and new biophysical approaches are providing unprecedented new insight into the membrane fusion reaction.

scholarly journals A glycosylated peptide in the West Nile virus envelope protein is immunogenic during equine infection

2008 ◽  
Vol 89 (12) ◽  
pp. 3063-3072 ◽  
Author(s):  
Jody Hobson-Peters ◽  
Philip Toye ◽  
Melissa D. Sánchez ◽  
Katharine N. Bossart ◽  
Lin-Fa Wang ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Fusion Protein ◽  
Synthetic Peptides ◽  
Mammalian Cells ◽  
Protein Glycosylation ◽  
The West ◽  
West Nile ◽  
High Sequence Identity ◽  
Recombinant Peptide ◽  
E Protein

Using a monoclonal antibody directed to domain I of the West Nile virus (WNV) envelope (E) protein, we identified a continuous (linear) epitope that was immunogenic during WNV infection of horses. Using synthetic peptides, this epitope was mapped to a 19 aa sequence (WN19: E147–165) encompassing the WNV NY99 E protein glycosylation site at position 154. The inability of WNV-positive horse and mouse sera to bind the synthetic peptides indicated that glycosylation was required for recognition of peptide WN19 by WNV-specific antibodies in sera. N-linked glycosylation of WN19 was achieved through expression of the peptide as a C-terminal fusion protein in mammalian cells and specific reactivity of WNV-positive horse sera to the glycosylated WN19 fusion protein was shown by Western blot. Additional sera collected from horses infected with Murray Valley encephalitis virus (MVEV), which is similarly glycosylated at position E154 and exhibits high sequence identity to WNV NY99 in this region, also recognized the recombinant peptide. Failure of most WNV- and MVEV-positive horse sera to recognize the epitope as a deglycosylated fusion protein confirmed that the N-linked glycan was important for antibody recognition of the peptide. Together, these results suggest that the induction of antibodies to the WN19 epitope during WNV infection of horses is generally associated with E protein glycosylation of the infecting viral strain.

Peptide models for the membrane destabilizing actions of viral fusion proteins

Biopolymers ◽  
1992 ◽  
Vol 32 (4) ◽  
pp. 309-314 ◽  
Author(s):  
Richard M. Epand ◽  
James J. Cheetham ◽  
Raquel F. Epand ◽  
Philip L. Yeagle ◽  
Christopher D. Richardson ◽  
...  
Keyword(s):  
Fusion Proteins ◽  
Viral Fusion ◽  
Peptide Models ◽  
Viral Fusion Proteins
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