Macrodomains: Structure, Function, Evolution, and Catalytic Activities

Rack, J.G.M.; Perina, Dragutin; Ahel, Ivan

doi:10.1146/annurev-biochem-060815-014935

Cited by 197 publications

(307 citation statements)

References 151 publications

(243 reference statements)

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“…3 D ). Our data showed that a major by-product of hydrolytic reaction is ADP-ribose, as seen for other macrodomain hydrolases (12). However, because the catalytic residues found in other macrodomain proteins such as TARG1 are not conserved in SCO6735 (Fig.…”

Section: Resultssupporting

confidence: 86%

“…Two of three macrodomain proteins have predicted functions. The SCO0909 protein of S. coelicolor is a bacterial-type PARG, predicted to remove poly-ADP-ribosylation (6); whereas SCO6450 is a macrodomain protein predicted to remove mono-ADP-ribosylation, it is a homologue of the MacroD proteins, which are present in representatives from all three domains of life (10, 12). We focused our research on the third macrodomain protein, SCO6735.…”

Section: Resultsmentioning

confidence: 99%

“…TARG1, MacroD1/2, and PARG represent different subgroups within the macrodomain protein family (10). Macrodomains are ancient folds with high affinity for ADP-ribose binding (11, 12). These three macrodomain subgroups use the macrodomain for catalysis but with distinct mechanisms (reviewed in Ref.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of Macrodomain Protein SCO6735 Increases Antibiotic Production in Streptomyces coelicolor

Lalić¹,

Marjanović²,

Palazzo

et al. 2016

Journal of Biological Chemistry

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ADP-ribosylation is a post-translational modification that can alter the physical and chemical properties of target proteins and that controls many important cellular processes. Macrodomains are evolutionarily conserved structural domains that bind ADP-ribose derivatives and are found in proteins with diverse cellular functions. Some proteins from the macrodomain family can hydrolyze ADP-ribosylated substrates and therefore reverse this post-translational modification. Bacteria and Streptomyces, in particular, are known to utilize protein ADP-ribosylation, yet very little is known about their enzymes that synthesize and remove this modification. We have determined the crystal structure and characterized, both biochemically and functionally, the macrodomain protein SCO6735 from Streptomyces coelicolor. This protein is a member of an uncharacterized subfamily of macrodomain proteins. Its crystal structure revealed a highly conserved macrodomain fold. We showed that SCO6735 possesses the ability to hydrolyze PARP-dependent protein ADP-ribosylation. Furthermore, we showed that expression of this protein is induced upon DNA damage and that deletion of this protein in S. coelicolor increases antibiotic production. Our results provide the first insights into the molecular basis of its action and impact on Streptomyces metabolism.

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

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Disruption of Macrodomain Protein SCO6735 Increases Antibiotic Production in Streptomyces coelicolor

Lalić¹,

Marjanović²,

Palazzo

et al. 2016

Journal of Biological Chemistry

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“…Macrodomains are larger (∼130-to 190-amino acid) globular domains that can bind to ("read") an ADP-ribose monomer or the terminal ADP-ribose moiety in a PAR chain (Table 1; Fig. 2A,B; Karras et al 2005;Feijs et al 2013;Rack et al 2016). The PBZs are short modules (∼30 amino acids) with the con-…”

Section: Arbds: Adp-ribose Readersmentioning

confidence: 99%

“…Other ARBDs include (1) the phosphopeptide-binding FHA and BRCT domains, (2) RRMs, and (3) RGGs (also called GAR domains) (Li et al 2013;Teloni and Altmeyer 2016). a See Kalisch et al (2012), Feijs et al (2013), Krietsch et al (2013), Hottiger (2015), Teloni and Altmeyer (2016), and Rack et al (2016) as well as references therein for a more comprehensive listing of ARBDs. 2006), PAR glycohydrolase (PARG) (Slade et al 2011), TARG/C6orf130 (Sharifi et al 2013), MacroD1 and MacroD2 Rosenthal et al 2013), and the NUDIX family of hydrolases (Daniels et al 2015b).…”

Section: Adp-ribose and Par Hydrolases: Erasersmentioning

confidence: 99%

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

2017

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The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.ADP-ribosylation is a reversible post-translational modification (PTM) of proteins resulting in the covalent attachment of a single ADP-ribose unit [i.e., mono(ADP-ribose) (MAR)] or polymers of ADP-ribose units [i.e., poly(ADP-ribose) (PAR)] on a variety of amino acid residues on target proteins (Gibson and Kraus 2012;Daniels et al. 2015a). This modification is mediated by a diverse group of ADPribosyl transferase (ADPRT) enzymes that use ADP-ribose units derived from β-NAD + to catalyze the ADP-ribosylation reaction. These enzymes include bacterial ADPRTs (e.g., cholera toxin and diphtheria toxin) as well as members of three different protein families in yeast and animals: (1) arginine-specific ecto-enzymes (ARTCs), (2) sirtuins, and (3) PAR polymerases (PARPs) . Surprisingly, a recent study showed that the bacterial toxin DarTG can ADP-ribosylate DNA . How this fits into the broader picture of cellular ADP-ribosylation has yet to be determined.In this review, we focus on the mono(ADP-ribosyl)ation (MARylation) and poly(ADP-ribosyl)ation (PARylation) of glutamate, aspartate, and lysine residues by PARP family members. While many reviews have been written on PARPs in the past decade, we highlight the current trends and ideas in the field, in particular those discoveries that have been published in the past 2-3 years.

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Robust immunoglobulin class switch recombination and end joining in Parp9‐deficient mice

et al. 2017

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To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving poly(ADP-ribose) polymerases Parp1, Parp2, and Parp3 to promote appropriate DNA repair and efficient long-range recombination. The macroParp Parp9, which is overexpressed in certain lymphomas, has been recently implicated in DSB repair, acting together with Parp1. Here, we examine the contribution of Parp9 to the resolution of physiological DSBs incurred during V(D)J recombination and CSR by generating Parp9 mice. We find that Parp9-deficient mice are viable, fertile, and do not show any overt phenotype. Moreover, we find that Parp9 is dispensable for B-cell development. Finally, we show that CSR and DNA end-joining are robust in the absence of Parp9, indicating that Parp9 is not essential in vivo to achieve physiological DSB repair, or that strong compensatory mechanisms exist.

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Macrodomains: Structure, Function, Evolution, and Catalytic Activities

Cited by 197 publications

References 151 publications

Disruption of Macrodomain Protein SCO6735 Increases Antibiotic Production in Streptomyces coelicolor

Disruption of Macrodomain Protein SCO6735 Increases Antibiotic Production in Streptomyces coelicolor

PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes

Robust immunoglobulin class switch recombination and end joining in Parp9‐deficient mice

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