A post-translational modification of human Norovirus capsid protein attenuates glycan binding

Alvaro Mallagaray; Robert Creutznacher; Jasmin Dülfer; Philipp H O Mayer; Lena Lisbeth Grimm; Jose Maria Orduña; Esben Trabjerg; Thilo Stehle; Kasper D Rand; Bärbel S Blaum; Charlotte Uetrecht; Thomas Peters

doi:10.1038/s41467-019-09251-5

A post-translational modification of human Norovirus capsid protein attenuates glycan binding

Alvaro Mallagaray, Robert Creutznacher, Jasmin Dülfer, Philipp H O Mayer, Lena Lisbeth Grimm, Jose Maria Orduña, Esben Trabjerg, Thilo Stehle, Kasper D Rand, Bärbel S Blaum, Charlotte Uetrecht, Thomas Peters

25 Citations (Scopus)

16 Downloads (Pure)

Abstract

Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.

Original language	English
Article number	1320
Journal	Nature Communications
Volume	10
Issue number	1
Number of pages	14
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-019-09251-5
Publication status	Published - 1 Dec 2019

Keywords

Asparagine/chemistry
Binding Sites
Blood Group Antigens/chemistry
Capsid Proteins/chemistry
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli/genetics
Gene Expression
Genetic Vectors/chemistry
Host-Pathogen Interactions
Humans
Isoaspartic Acid/chemistry
Kinetics
Models, Molecular
Norovirus/genetics
Polysaccharides/chemistry
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Protein Processing, Post-Translational
Recombinant Proteins/chemistry

Access to Document

10.1038/s41467-019-09251-5Licence: CC BY

s41467-019-09251-5Final published version, 3.26 MBLicence: CC BY

Cite this

@article{314f8a4afcb54db4afa4bb3806550686,

title = "A post-translational modification of human Norovirus capsid protein attenuates glycan binding",

abstract = "Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.",

keywords = "Asparagine/chemistry, Binding Sites, Blood Group Antigens/chemistry, Capsid Proteins/chemistry, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli/genetics, Gene Expression, Genetic Vectors/chemistry, Host-Pathogen Interactions, Humans, Isoaspartic Acid/chemistry, Kinetics, Models, Molecular, Norovirus/genetics, Polysaccharides/chemistry, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Multimerization, Protein Processing, Post-Translational, Recombinant Proteins/chemistry",

author = "Alvaro Mallagaray and Robert Creutznacher and Jasmin D{\"u}lfer and Mayer, {Philipp H O} and Grimm, {Lena Lisbeth} and Ordu{\~n}a, {Jose Maria} and Esben Trabjerg and Thilo Stehle and Rand, {Kasper D} and Blaum, {B{\"a}rbel S} and Charlotte Uetrecht and Thomas Peters",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-09251-5",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

TY - JOUR

T1 - A post-translational modification of human Norovirus capsid protein attenuates glycan binding

AU - Mallagaray, Alvaro

AU - Creutznacher, Robert

AU - Dülfer, Jasmin

AU - Mayer, Philipp H O

AU - Grimm, Lena Lisbeth

AU - Orduña, Jose Maria

AU - Trabjerg, Esben

AU - Stehle, Thilo

AU - Rand, Kasper D

AU - Blaum, Bärbel S

AU - Uetrecht, Charlotte

AU - Peters, Thomas

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.

AB - Attachment of human noroviruses to histo blood group antigens (HBGAs) is essential for infection, but how this binding event promotes the infection of host cells is unknown. Here, we employ protein NMR experiments supported by mass spectrometry and crystallography to study HBGA binding to the P-domain of a prevalent virus strain (GII.4). We report a highly selective transformation of asparagine 373, located in an antigenic loop adjoining the HBGA binding site, into an iso-aspartate residue. This spontaneous post-translational modification (PTM) proceeds with an estimated half-life of a few days at physiological temperatures, independent of the presence of HBGAs but dramatically affecting HBGA recognition. Sequence conservation and the surface-exposed position of this PTM suggest an important role in infection and immune recognition for many norovirus strains.

KW - Asparagine/chemistry

KW - Binding Sites

KW - Blood Group Antigens/chemistry

KW - Capsid Proteins/chemistry

KW - Cloning, Molecular

KW - Crystallography, X-Ray

KW - Escherichia coli/genetics

KW - Gene Expression

KW - Genetic Vectors/chemistry

KW - Host-Pathogen Interactions

KW - Humans

KW - Isoaspartic Acid/chemistry

KW - Kinetics

KW - Models, Molecular

KW - Norovirus/genetics

KW - Polysaccharides/chemistry

KW - Protein Binding

KW - Protein Conformation, alpha-Helical

KW - Protein Conformation, beta-Strand

KW - Protein Interaction Domains and Motifs

KW - Protein Multimerization

KW - Protein Processing, Post-Translational

KW - Recombinant Proteins/chemistry

U2 - 10.1038/s41467-019-09251-5

DO - 10.1038/s41467-019-09251-5

M3 - Journal article

C2 - 30899001

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1320

ER -

A post-translational modification of human Norovirus capsid protein attenuates glycan binding

Abstract

Keywords

Access to Document

Fingerprint

Cite this