Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family

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

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Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family. / Trempe, Jean-François; Šašková, Klára Grantz; Sivá, Monika; Ratcliffe, Colin D H; Veverka, Václav; Hoegl, Annabelle; Ménade, Marie; Feng, Xin; Shenker, Solomon; Svoboda, Michal; Kožíšek, Milan; Konvalinka, Jan; Gehring, Kalle.

In: Scientific Reports, Vol. 6, 20.09.2016, p. 33671.

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

Harvard

Trempe, J-F, Šašková, KG, Sivá, M, Ratcliffe, CDH, Veverka, V, Hoegl, A, Ménade, M, Feng, X, Shenker, S, Svoboda, M, Kožíšek, M, Konvalinka, J & Gehring, K 2016, 'Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family', Scientific Reports, vol. 6, pp. 33671. https://doi.org/10.1038/srep33671

APA

Trempe, J-F., Šašková, K. G., Sivá, M., Ratcliffe, C. D. H., Veverka, V., Hoegl, A., Ménade, M., Feng, X., Shenker, S., Svoboda, M., Kožíšek, M., Konvalinka, J., & Gehring, K. (2016). Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family. Scientific Reports, 6, 33671. https://doi.org/10.1038/srep33671

Vancouver

Trempe J-F, Šašková KG, Sivá M, Ratcliffe CDH, Veverka V, Hoegl A et al. Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family. Scientific Reports. 2016 Sep 20;6:33671. https://doi.org/10.1038/srep33671

Author

Trempe, Jean-François ; Šašková, Klára Grantz ; Sivá, Monika ; Ratcliffe, Colin D H ; Veverka, Václav ; Hoegl, Annabelle ; Ménade, Marie ; Feng, Xin ; Shenker, Solomon ; Svoboda, Michal ; Kožíšek, Milan ; Konvalinka, Jan ; Gehring, Kalle. / Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family. In: Scientific Reports. 2016 ; Vol. 6. pp. 33671.

Bibtex

@article{b8d1192746d9456da93e0858c777e724,
title = "Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family",
abstract = "The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.",
keywords = "Amino Acid Sequence, Binding Sites, Catalytic Domain, Crystallography, X-Ray, DNA Damage, Models, Molecular, Multigene Family, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Proteomics/methods, Saccharomyces cerevisiae/genetics, Saccharomyces cerevisiae Proteins/chemistry, Substrate Specificity, Ubiquitin/metabolism",
author = "Jean-Fran{\c c}ois Trempe and {\v S}a{\v s}kov{\'a}, {Kl{\'a}ra Grantz} and Monika Siv{\'a} and Ratcliffe, {Colin D H} and V{\'a}clav Veverka and Annabelle Hoegl and Marie M{\'e}nade and Xin Feng and Solomon Shenker and Michal Svoboda and Milan Ko{\v z}{\'i}{\v s}ek and Jan Konvalinka and Kalle Gehring",
year = "2016",
month = sep,
day = "20",
doi = "10.1038/srep33671",
language = "English",
volume = "6",
pages = "33671",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family

AU - Trempe, Jean-François

AU - Šašková, Klára Grantz

AU - Sivá, Monika

AU - Ratcliffe, Colin D H

AU - Veverka, Václav

AU - Hoegl, Annabelle

AU - Ménade, Marie

AU - Feng, Xin

AU - Shenker, Solomon

AU - Svoboda, Michal

AU - Kožíšek, Milan

AU - Konvalinka, Jan

AU - Gehring, Kalle

PY - 2016/9/20

Y1 - 2016/9/20

N2 - The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.

AB - The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.

KW - Amino Acid Sequence

KW - Binding Sites

KW - Catalytic Domain

KW - Crystallography, X-Ray

KW - DNA Damage

KW - Models, Molecular

KW - Multigene Family

KW - Protein Binding

KW - Protein Conformation

KW - Protein Interaction Domains and Motifs

KW - Proteomics/methods

KW - Saccharomyces cerevisiae/genetics

KW - Saccharomyces cerevisiae Proteins/chemistry

KW - Substrate Specificity

KW - Ubiquitin/metabolism

U2 - 10.1038/srep33671

DO - 10.1038/srep33671

M3 - Journal article

C2 - 27646017

VL - 6

SP - 33671

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -

ID: 209575382