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Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein

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Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein. / Karlberg, Tobias; Klepsch, Mirjam; Thorsell, Ann-Gerd; Andersson, C David; Linusson, Anna; Schüler, Herwig.

In: J BIOL CHEM, Vol. 290, No. 12, 20.03.2015, p. 7336-44.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Karlberg, T, Klepsch, M, Thorsell, A-G, Andersson, CD, Linusson, A & Schüler, H 2015, 'Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein', J BIOL CHEM, vol. 290, no. 12, pp. 7336-44. https://doi.org/10.1074/jbc.M114.630160

APA

Karlberg, T., Klepsch, M., Thorsell, A-G., Andersson, C. D., Linusson, A., & Schüler, H. (2015). Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein. J BIOL CHEM, 290(12), 7336-44. https://doi.org/10.1074/jbc.M114.630160

Vancouver

Karlberg T, Klepsch M, Thorsell A-G, Andersson CD, Linusson A, Schüler H. Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein. J BIOL CHEM. 2015 Mar 20;290(12):7336-44. https://doi.org/10.1074/jbc.M114.630160

Bibtex

@article{b8ad980b4edc4951be544d7250ca8955,
title = "Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein",
abstract = "The mammalian poly(ADP-ribose) polymerase (PARP) family includes ADP-ribosyltransferases with diphtheria toxin homology (ARTD). Most members have mono-ADP-ribosyltransferase activity. PARP13/ARTD13, also called zinc finger antiviral protein, has roles in viral immunity and microRNA-mediated stress responses. PARP13 features a divergent PARP homology domain missing a PARP consensus sequence motif; the domain has enigmatic functions and apparently lacks catalytic activity. We used x-ray crystallography, molecular dynamics simulations, and biochemical analyses to investigate the structural requirements for ADP-ribosyltransferase activity in human PARP13 and two of its functional partners in stress granules: PARP12/ARTD12, and PARP15/BAL3/ARTD7. The crystal structure of the PARP homology domain of PARP13 shows obstruction of the canonical active site, precluding NAD(+) binding. Molecular dynamics simulations indicate that this closed cleft conformation is maintained in solution. Introducing consensus side chains in PARP13 did not result in 3-aminobenzamide binding, but in further closure of the site. Three-dimensional alignment of the PARP homology domains of PARP13, PARP12, and PARP15 illustrates placement of PARP13 residues that deviate from the PARP family consensus. Introducing either one of two of these side chains into the corresponding positions in PARP15 abolished PARP15 ADP-ribosyltransferase activity. Taken together, our results show that PARP13 lacks the structural requirements for ADP-ribosyltransferase activity.",
keywords = "ADP Ribose Transferases, Amino Acid Sequence, Crystallography, X-Ray, Humans, Molecular Dynamics Simulation, Molecular Sequence Data, Mutagenesis, Site-Directed, NAD, Poly(ADP-ribose) Polymerases, Sequence Homology, Amino Acid, Zinc Fingers, Journal Article, Research Support, Non-U.S. Gov't",
author = "Tobias Karlberg and Mirjam Klepsch and Ann-Gerd Thorsell and Andersson, {C David} and Anna Linusson and Herwig Sch{\"u}ler",
note = "{\textcopyright} 2015 by The American Society for Biochemistry and Molecular Biology, Inc.",
year = "2015",
month = mar,
day = "20",
doi = "10.1074/jbc.M114.630160",
language = "English",
volume = "290",
pages = "7336--44",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Structural basis for lack of ADP-ribosyltransferase activity in poly(ADP-ribose) polymerase-13/zinc finger antiviral protein

AU - Karlberg, Tobias

AU - Klepsch, Mirjam

AU - Thorsell, Ann-Gerd

AU - Andersson, C David

AU - Linusson, Anna

AU - Schüler, Herwig

N1 - © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

PY - 2015/3/20

Y1 - 2015/3/20

N2 - The mammalian poly(ADP-ribose) polymerase (PARP) family includes ADP-ribosyltransferases with diphtheria toxin homology (ARTD). Most members have mono-ADP-ribosyltransferase activity. PARP13/ARTD13, also called zinc finger antiviral protein, has roles in viral immunity and microRNA-mediated stress responses. PARP13 features a divergent PARP homology domain missing a PARP consensus sequence motif; the domain has enigmatic functions and apparently lacks catalytic activity. We used x-ray crystallography, molecular dynamics simulations, and biochemical analyses to investigate the structural requirements for ADP-ribosyltransferase activity in human PARP13 and two of its functional partners in stress granules: PARP12/ARTD12, and PARP15/BAL3/ARTD7. The crystal structure of the PARP homology domain of PARP13 shows obstruction of the canonical active site, precluding NAD(+) binding. Molecular dynamics simulations indicate that this closed cleft conformation is maintained in solution. Introducing consensus side chains in PARP13 did not result in 3-aminobenzamide binding, but in further closure of the site. Three-dimensional alignment of the PARP homology domains of PARP13, PARP12, and PARP15 illustrates placement of PARP13 residues that deviate from the PARP family consensus. Introducing either one of two of these side chains into the corresponding positions in PARP15 abolished PARP15 ADP-ribosyltransferase activity. Taken together, our results show that PARP13 lacks the structural requirements for ADP-ribosyltransferase activity.

AB - The mammalian poly(ADP-ribose) polymerase (PARP) family includes ADP-ribosyltransferases with diphtheria toxin homology (ARTD). Most members have mono-ADP-ribosyltransferase activity. PARP13/ARTD13, also called zinc finger antiviral protein, has roles in viral immunity and microRNA-mediated stress responses. PARP13 features a divergent PARP homology domain missing a PARP consensus sequence motif; the domain has enigmatic functions and apparently lacks catalytic activity. We used x-ray crystallography, molecular dynamics simulations, and biochemical analyses to investigate the structural requirements for ADP-ribosyltransferase activity in human PARP13 and two of its functional partners in stress granules: PARP12/ARTD12, and PARP15/BAL3/ARTD7. The crystal structure of the PARP homology domain of PARP13 shows obstruction of the canonical active site, precluding NAD(+) binding. Molecular dynamics simulations indicate that this closed cleft conformation is maintained in solution. Introducing consensus side chains in PARP13 did not result in 3-aminobenzamide binding, but in further closure of the site. Three-dimensional alignment of the PARP homology domains of PARP13, PARP12, and PARP15 illustrates placement of PARP13 residues that deviate from the PARP family consensus. Introducing either one of two of these side chains into the corresponding positions in PARP15 abolished PARP15 ADP-ribosyltransferase activity. Taken together, our results show that PARP13 lacks the structural requirements for ADP-ribosyltransferase activity.

KW - ADP Ribose Transferases

KW - Amino Acid Sequence

KW - Crystallography, X-Ray

KW - Humans

KW - Molecular Dynamics Simulation

KW - Molecular Sequence Data

KW - Mutagenesis, Site-Directed

KW - NAD

KW - Poly(ADP-ribose) Polymerases

KW - Sequence Homology, Amino Acid

KW - Zinc Fingers

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1074/jbc.M114.630160

DO - 10.1074/jbc.M114.630160

M3 - SCORING: Journal article

C2 - 25635049

VL - 290

SP - 7336

EP - 7344

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 12

ER -