Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

Ping Yuan; George P. Leser; Borries Demeler; Robert A. Lamb; Theodore S. Jardetzky

doi:10.1016/j.virol.2008.05.023

Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

Ping Yuan, George P. Leser, Borries Demeler, Robert A. Lamb, Theodore S. Jardetzky^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high α-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

Original language	English (US)
Pages (from-to)	282-291
Number of pages	10
Journal	Virology
Volume	378
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2008.05.023
State	Published - Sep 1 2008

Funding

We thank past and present members of the Jardetzky and Lamb Laboratories. This research was supported in part by NIH research grants to T.S.J. (GM-61050) and R.A.L. (AI-23173). R.A.L. is an Investigator of the Howard Hughes Medical Institute. We thankfully acknowledge the use of instruments in the Keck Biophysics Facility at Northwestern University [ http://www.biochem.northwestern.edu/Keck/keckmain.html ]. We would also like to acknowledge support for the development of the UltraScan software by NIH 1 R01 RR022200-01A1 (B.D.), the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation (B.D.), NSF TGMCB070038 (B.D.), and CAUMA facility support through NCI Grant P30 CA054174 and UTHSCSA ERC.

Keywords

Hemagglutinin-neuraminidase (HN)
Membrane fusion/HN stalk
Parainfluenza virus 5
Paramyxovirus
Sialic acid
Virus entry

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2008.05.023

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@article{03e3b08e7e6b4819b4467824a089662a,

title = "Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein",

abstract = "The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high α-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.",

keywords = "Hemagglutinin-neuraminidase (HN), Membrane fusion/HN stalk, Parainfluenza virus 5, Paramyxovirus, Sialic acid, Virus entry",

author = "Ping Yuan and Leser, \{George P.\} and Borries Demeler and Lamb, \{Robert A.\} and Jardetzky, \{Theodore S.\}",

note = "Funding Information: We thank past and present members of the Jardetzky and Lamb Laboratories. This research was supported in part by NIH research grants to T.S.J. (GM-61050) and R.A.L. (AI-23173). R.A.L. is an Investigator of the Howard Hughes Medical Institute. We thankfully acknowledge the use of instruments in the Keck Biophysics Facility at Northwestern University [ http://www.biochem.northwestern.edu/Keck/keckmain.html ]. We would also like to acknowledge support for the development of the UltraScan software by NIH 1 R01 RR022200-01A1 (B.D.), the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation (B.D.), NSF TGMCB070038 (B.D.), and CAUMA facility support through NCI Grant P30 CA054174 and UTHSCSA ERC. ",

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doi = "10.1016/j.virol.2008.05.023",

language = "English (US)",

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T1 - Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

AU - Yuan, Ping

AU - Leser, George P.

AU - Demeler, Borries

AU - Lamb, Robert A.

AU - Jardetzky, Theodore S.

N1 - Funding Information: We thank past and present members of the Jardetzky and Lamb Laboratories. This research was supported in part by NIH research grants to T.S.J. (GM-61050) and R.A.L. (AI-23173). R.A.L. is an Investigator of the Howard Hughes Medical Institute. We thankfully acknowledge the use of instruments in the Keck Biophysics Facility at Northwestern University [ http://www.biochem.northwestern.edu/Keck/keckmain.html ]. We would also like to acknowledge support for the development of the UltraScan software by NIH 1 R01 RR022200-01A1 (B.D.), the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation (B.D.), NSF TGMCB070038 (B.D.), and CAUMA facility support through NCI Grant P30 CA054174 and UTHSCSA ERC.

PY - 2008/9/1

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N2 - The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high α-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

AB - The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high α-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

KW - Hemagglutinin-neuraminidase (HN)

KW - Membrane fusion/HN stalk

KW - Parainfluenza virus 5

KW - Paramyxovirus

KW - Sialic acid

KW - Virus entry

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JF - Virology

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ER -

Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

Abstract

Funding

Keywords

ASJC Scopus subject areas

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