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Title: Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk

Abstract

The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid receptors, activating the fusion (F) protein to activate membrane fusion and viral entry, and cleaving sialic acid from carbohydrate chains. HN is an oligomeric integral membrane protein consisting of an N-terminal transmembrane domain, a stalk region, and an enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains have been solved previously; however, the structure of the stalk region has remained elusive. The stalk region contains specificity determinants for F interactions and activation, underlying the requirement for homotypic F and HN interactions in viral entry. Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F activation and NA activities, but a structural basis for understanding these dual affects on HN functions has been lacking. Here, we report the structure of the Newcastle disease virus HN ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that allows classification of extensive mutational data, providing insight into the functional roles of the stalk region. Mutations that affect both F activation and NA activities map predominantly tomore » the 4HB hydrophobic core, whereas mutations that affect only F-protein activation map primarily to the 4HB surface. Two of four NA domains interact with the 4HB stalk, and residues at this interface in both the stalk and NA domain have been implicated in HN function.« less

Authors:
; ; ; ; ;  [1]
  1. Stanford-MED
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1031382
Resource Type:
Journal Article
Journal Name:
Proc. Natl. Acad. Sci. USA
Additional Journal Information:
Journal Volume: 108; Journal Issue: (36) ; 09, 2011; Journal ID: ISSN 0027-8424
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; CARBOHYDRATES; CHAINS; CLASSIFICATION; DIMERS; FUNCTIONALS; MEMBRANE PROTEINS; MEMBRANES; MUTATIONS; NEWCASTLE DISEASE; PROTEINS; RESIDUES; SIALIC ACID; SPECIFICITY

Citation Formats

Yuan, Ping, Swanson, Kurt A., Leser, George P., Paterson, Reay G., Lamb, Robert A., Jardetzky, Theodore S., and NWU). Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk. United States: N. p., 2014. Web. doi:10.1073/pnas.1111691108.
Yuan, Ping, Swanson, Kurt A., Leser, George P., Paterson, Reay G., Lamb, Robert A., Jardetzky, Theodore S., & NWU). Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk. United States. https://doi.org/10.1073/pnas.1111691108
Yuan, Ping, Swanson, Kurt A., Leser, George P., Paterson, Reay G., Lamb, Robert A., Jardetzky, Theodore S., and NWU). Thu . "Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk". United States. https://doi.org/10.1073/pnas.1111691108.
@article{osti_1031382,
title = {Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk},
author = {Yuan, Ping and Swanson, Kurt A. and Leser, George P. and Paterson, Reay G. and Lamb, Robert A. and Jardetzky, Theodore S. and NWU)},
abstractNote = {The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid receptors, activating the fusion (F) protein to activate membrane fusion and viral entry, and cleaving sialic acid from carbohydrate chains. HN is an oligomeric integral membrane protein consisting of an N-terminal transmembrane domain, a stalk region, and an enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains have been solved previously; however, the structure of the stalk region has remained elusive. The stalk region contains specificity determinants for F interactions and activation, underlying the requirement for homotypic F and HN interactions in viral entry. Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F activation and NA activities, but a structural basis for understanding these dual affects on HN functions has been lacking. Here, we report the structure of the Newcastle disease virus HN ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that allows classification of extensive mutational data, providing insight into the functional roles of the stalk region. Mutations that affect both F activation and NA activities map predominantly to the 4HB hydrophobic core, whereas mutations that affect only F-protein activation map primarily to the 4HB surface. Two of four NA domains interact with the 4HB stalk, and residues at this interface in both the stalk and NA domain have been implicated in HN function.},
doi = {10.1073/pnas.1111691108},
url = {https://www.osti.gov/biblio/1031382}, journal = {Proc. Natl. Acad. Sci. USA},
issn = {0027-8424},
number = (36) ; 09, 2011,
volume = 108,
place = {United States},
year = {2014},
month = {10}
}