Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion

doi:https://doi.org/10.1128/JVI.06350-11

Title: Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion

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Abstract

Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 {angstrom}, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylatedmore »« less

Authors:

Bose, Sayantan; Welch, Brett D.; Kors, Christopher A.; Yuan, Ping; Jardetzky, Theodore S.; Lamb, Robert A. ^[1]

Publication Date:: 2014-10-02

Research Org.:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: National Institutes of Health (NIH)

OSTI Identifier:: 1050071

Resource Type:: Journal Article

Journal Name:: J. Virol.

Additional Journal Information:: Journal Volume: 85; Journal Issue: (24) ; 12, 2011; Journal ID: ISSN 0022-538X

Country of Publication:: United States

Language:: ENGLISH

Subject:: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ACTIVATION ENERGY; CRYSTAL STRUCTURE; DISULFIDES; ELECTRON DENSITY; MEMBRANES; MUTAGENESIS; MUTANTS; PROTEINS; RESIDUES; RESOLUTION

Citation Formats


                    Bose, Sayantan, Welch, Brett D., Kors, Christopher A., Yuan, Ping, Jardetzky, Theodore S., Lamb, Robert A., and Stanford-MED). Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion.  United States: N. p., 2014. 
        Web.  doi:10.1128/JVI.06350-11.

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                    Bose, Sayantan, Welch, Brett D., Kors, Christopher A., Yuan, Ping, Jardetzky, Theodore S., Lamb, Robert A., & Stanford-MED). Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion.  United States.  https://doi.org/10.1128/JVI.06350-11

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                    Bose, Sayantan, Welch, Brett D., Kors, Christopher A., Yuan, Ping, Jardetzky, Theodore S., Lamb, Robert A., and Stanford-MED). Thu .  
        "Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion".  United States.  https://doi.org/10.1128/JVI.06350-11.

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@article{osti_1050071,

  title        = {Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion},

  author       = {Bose, Sayantan and Welch, Brett D. and Kors, Christopher A. and Yuan, Ping and Jardetzky, Theodore S. and Lamb, Robert A. and Stanford-MED)},

  abstractNote = {Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 {angstrom}, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.},

  doi          = {10.1128/JVI.06350-11},

  url          = {https://www.osti.gov/biblio/1050071},
  journal      = {J. Virol.},

  issn         = {0022-538X},

  number       = (24) ; 12, 2011,

  volume       = 85,

  place        = {United States},

  year         = {2014},

  month        = {10}

}

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