H
IPR043472

Macro domain-like

InterPro entry
Short nameMacro_dom-like
Overlapping entries
 
Macro domain (IPR002589)
Macro-like domain (IPR028071)

Description

The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent
[4]
: in certain cases it is believed to bind non-covalently
[2]
; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein
[5]
. The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein
[9]
. The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A
[3, 8]
. Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses
[16, 17]
, Rubella and Hepatitis E viruses. In vertebrates the domain occurs e.g. in histone macroH2A, in predicted poly-ADP-ribose polymerases (PARPs) and in B aggressive lymphoma (BAL) protein. The macro domain can be associated with catalytic domains, such as PARP, or sirtuin. The Macro domain can recognise ADP-ribose or in some cases poly-ADP-ribose, which can be involved in ADP-ribosylation reactions that occur in important processes, such as chromatin biology, DNA repair and transcription regulation
[6]
. The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose
[7]
. The Macro domain has been suggested to play a regulatory role in ADP-ribosylation, which is involved in inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis.

The 3D structure of the SARS-CoV Macro domain has a mixed α/β fold consisting of a central seven-stranded twisted mixed β-sheet sandwiched between two α-helices on one face, and three on the other. The final α-helix, located on the edge of the central β-sheet, forms the C terminus of the protein
[1]
. The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the β-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site
[8, 6, 7, 1]
.

Aminopeptidases are exopeptidases involved in the processing and regular turnover of intracellular proteins, although their precise role in cellular metabolism is unclear
[13, 14]
.

Leucine aminopeptidases cleave leucine residues from the N-terminal of polypeptide chains; in general they are involved in the processing, catabolism and degradation of intracellular proteins
[11, 13, 14]
. Leucyl aminopeptidase forms a homohexamer containing two trimers stacked on top of one another
[14]
. Each monomer binds two zinc ions. The zinc-binding and catalytic sites are located within the C-terminal catalytic domain
[14]
. Leucine aminopeptidase has been shown to be identical with prolyl aminopeptidase (
3.4.11.5
) in mammals
[12]
.

The N-terminal domain of these proteins has been shown in Escherichia coli PepA to function as a DNA-binding protein in Xer site-specific recombination and in transcriptional control of the carAB operon
[10, 15]
.

This superfamily represents the Macro domain as well as the N-terminal domain of Leucine aminopeptidase.

References

1.Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains. Egloff MP, Malet H, Putics A, Heinonen M, Dutartre H, Frangeul A, Gruez A, Campanacci V, Cambillau C, Ziebuhr J, Ahola T, Canard B. J. Virol. 80, 8493-502, (2006). View articlePMID: 16912299

2.Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites. Neuvonen M, Ahola T. J. Mol. Biol. 385, 212-25, (2009). View articlePMID: 18983849

3.The WWE domain: a common interaction module in protein ubiquitination and ADP ribosylation. Aravind L. Trends Biochem. Sci. 26, 273-5, (2001). View articlePMID: 11343911

4.Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Hassa PO, Haenni SS, Elser M, Hottiger MO. Microbiol. Mol. Biol. Rev. 70, 789-829, (2006). View articlePMID: 16959969

5.Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC. Nature 451, 81-5, (2008). View articlePMID: 18172500

6.The macro domain is an ADP-ribose binding module. Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG. EMBO J. 24, 1911-20, (2005). View articlePMID: 15902274

7.Splicing regulates NAD metabolite binding to histone macroH2A. Kustatscher G, Hothorn M, Pugieux C, Scheffzek K, Ladurner AG. Nat. Struct. Mol. Biol. 12, 624-5, (2005). View articlePMID: 15965484

8.The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A. Allen MD, Buckle AM, Cordell SC, Lowe J, Bycroft M. J. Mol. Biol. 330, 503-11, (2003). View articlePMID: 12842467

9.A biochemical genomics approach for identifying genes by the activity of their products. Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM. Science 286, 1153-5, (1999). View articlePMID: 10550052

10.X-ray structure of aminopeptidase A from Escherichia coli and a model for the nucleoprotein complex in Xer site-specific recombination. Strater N, Sherratt DJ, Colloms SD. EMBO J. 18, 4513-22, (1999). View articlePMID: 10449417

11.Bacterial aminopeptidases: properties and functions. Gonzales T, Robert-Baudouy J. FEMS Microbiol. Rev. 18, 319-44, (1996). View articlePMID: 8703509

12.Structural and immunological evidence for the identity of prolyl aminopeptidase with leucyl aminopeptidase. Matsushima M, Takahashi T, Ichinose M, Miki K, Kurokawa K, Takahashi K. Biochem. Biophys. Res. Commun. 178, 1459-64, (1991). View articlePMID: 1908238

13.Leucine aminopeptidase from Arabidopsis thaliana. Molecular evidence for a phylogenetically conserved enzyme of protein turnover in higher plants. Bartling D, Weiler EW. Eur. J. Biochem. 205, 425-31, (1992). View articlePMID: 1555602

14.Molecular structure of leucine aminopeptidase at 2.7-A resolution. Burley SK, David PR, Taylor A, Lipscomb WN. Proc. Natl. Acad. Sci. U.S.A. 87, 6878-82, (1990). View articlePMID: 2395881

15.Mutational analysis of Escherichia coli PepA, a multifunctional DNA-binding aminopeptidase. Charlier D, Kholti A, Huysveld N, Gigot D, Maes D, Thia-Toong TL, Glansdorff N. J. Mol. Biol. 302, 411-26, (2000). View articlePMID: 10970742

16.The ADP-ribose-1''-monophosphatase domains of severe acute respiratory syndrome coronavirus and human coronavirus 229E mediate resistance to antiviral interferon responses. Kuri T, Eriksson KK, Putics A, Zust R, Snijder EJ, Davidson AD, Siddell SG, Thiel V, Ziebuhr J, Weber F. J. Gen. Virol. 92, 1899-1905, (2011). PMID: 21525212

17.The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression. Grunewald ME, Chen Y, Kuny C, Maejima T, Lease R, Ferraris D, Aikawa M, Sullivan CS, Perlman S, Fehr AR. PLoS Pathog. 15, e1007756, (2019). PMID: 31095648

Cross References

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