Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography

Ana Sofia Ferreira-Ramos; Gerlind Sulzenbacher; Bruno Canard; Bruno Coutard

doi:10.1038/s41598-020-70870-w

Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography

Ana Sofia Ferreira-Ramos, Gerlind Sulzenbacher^*, Bruno Canard, Bruno Coutard

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Biochemie

Universität Aix-Marseille

9 Zitate (Scopus)

Abstract

Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised.

Originalsprache	Englisch
Aufsatznummer	14422
Zeitschrift	Scientific Reports
Jahrgang	10
Ausgabenummer	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-020-70870-w
Publikationsstatus	Veröffentlicht - 01.12.2020

Fördermittel

We thank the European Synchrotron Radiation Facility (ESRF) and Synchrotron Soleil for beamtime allocation, and the staff of beamlines Proxima2, ID23-1 and ID30A-3 for assistance with data collection. This work was supported by the European Union Horizon 2020 Marie Skłodowska-Curie ETN “ANTIVIRALS” (Grant Agreement Number 642434) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01. We thank Dr Karine Barral, Dr Sandrine Py and Dr Nicolas Papageorgiou for helpful discussions.

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

DFG-Fachsystematik

2.11-01 Biochemie

Dokumente

10.1038/s41598-020-70870-w

Weitere Links

Link to publication in Scopus

Zitieren

@article{2442627804ba4e72b842c7c6963dbb0c,

title = "Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography",

abstract = "Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised.",

author = "Ferreira-Ramos, \{Ana Sofia\} and Gerlind Sulzenbacher and Bruno Canard and Bruno Coutard",

note = "Funding Information: We thank the European Synchrotron Radiation Facility (ESRF) and Synchrotron Soleil for beamtime allocation, and the staff of beamlines Proxima2, ID23-1 and ID30A-3 for assistance with data collection. This work was supported by the European Union Horizon 2020 Marie Sk{\l}odowska-Curie ETN “ANTIVIRALS” (Grant Agreement Number 642434) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01. We thank Dr Karine Barral, Dr Sandrine Py and Dr Nicolas Papageorgiou for helpful discussions. Publisher Copyright: {\textcopyright} 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41598-020-70870-w",

language = "English",

volume = "10",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Springer Science and Business Media, LLC",

number = "1",

}

TY - JOUR

T1 - Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography

AU - Ferreira-Ramos, Ana Sofia

AU - Sulzenbacher, Gerlind

AU - Canard, Bruno

AU - Coutard, Bruno

N1 - Funding Information: We thank the European Synchrotron Radiation Facility (ESRF) and Synchrotron Soleil for beamtime allocation, and the staff of beamlines Proxima2, ID23-1 and ID30A-3 for assistance with data collection. This work was supported by the European Union Horizon 2020 Marie Skłodowska-Curie ETN “ANTIVIRALS” (Grant Agreement Number 642434) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01. We thank Dr Karine Barral, Dr Sandrine Py and Dr Nicolas Papageorgiou for helpful discussions. Publisher Copyright: © 2020, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised.

AB - Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised.

UR - https://www.scopus.com/pages/publications/85090081217

U2 - 10.1038/s41598-020-70870-w

DO - 10.1038/s41598-020-70870-w

M3 - Journal articles

C2 - 32879358

AN - SCOPUS:85090081217

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14422

ER -

Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography

Abstract

Fördermittel

UN SDGs

Strategische Forschungsbereiche und Zentren

DFG-Fachsystematik

Dokumente

Weitere Links

Fingerprint

Zitieren