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 [[cite:PUB00052327]]: in certain cases it is believed to bind non-covalently [[cite:PUB00052325]]; 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 [[cite:PUB00052328]]. This domain is found in a number of otherwise unrelated proteins. It is found at the C-terminus of the macro-H2A histone protein 4 and also in the non-structural proteins of several types of ssRNA viruses such as NSP3 from alpha-viruses and coronaviruses. This domain is also found on its own in a family of proteins from bacteria, archaebacteria and eukaryotes. The 3D structure of the SARS-CoV Macro domain has a mixed alpha/beta fold consisting of a central seven-stranded twisted mixed beta sheet sandwiched between two alpha helices on one face, and three on the other. The final alpha-helix, located on the edge of the central beta-sheet, forms the C terminus of the protein [[cite:PUB00043976]]. 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 beta-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site [[cite:PUB00021744]].
","llm":false,"checked":false,"updated":false}],"wikipedia":[{"title":"Macro_domain","extract":"In molecular biology, the Macro domain or A1pp domain is an ancient, evolutionary conserved structural module found in all kingdoms of life as well as some viruses. Macro domains are modules of about 180 amino acids that can bind ADP-ribose, an NAD metabolite, or related ligands. Binding to ADP-ribose can be either covalent or non-covalent: in certain cases it is believed to bind non-covalently, while in other cases it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein.
","thumbnail":null}],"literature":{"PUB00052325":{"PMID":18983849,"ISBN":null,"volume":"385","issue":"1","year":2009,"title":"Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites.","URL":null,"raw_pages":"212-25","medline_journal":"J Mol Biol","ISO_journal":"J. Mol. Biol.","authors":["Neuvonen M","Ahola T."],"DOI_URL":"http://dx.doi.org/10.1016/j.jmb.2008.10.045"},"PUB00043976":{"PMID":16912299,"ISBN":null,"volume":"80","issue":"17","year":2006,"title":"Structural and functional basis for ADP-ribose and poly(ADP-ribose) binding by viral macro domains.","URL":null,"raw_pages":"8493-502","medline_journal":"J Virol","ISO_journal":"J. Virol.","authors":["Egloff MP","Malet H","Putics A","Heinonen M","Dutartre H","Frangeul A","Gruez A","Campanacci V","Cambillau C","Ziebuhr J","Ahola T","Canard B."],"DOI_URL":"http://dx.doi.org/10.1128/JVI.00713-06"},"PUB00052327":{"PMID":16959969,"ISBN":null,"volume":"70","issue":"3","year":2006,"title":"Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?","URL":null,"raw_pages":"789-829","medline_journal":"Microbiol Mol Biol Rev","ISO_journal":"Microbiol. Mol. Biol. Rev.","authors":["Hassa PO","Haenni SS","Elser M","Hottiger MO."],"DOI_URL":"http://dx.doi.org/10.1128/MMBR.00040-05"},"PUB00052328":{"PMID":18172500,"ISBN":null,"volume":"451","issue":"7174","year":2008,"title":"Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins.","URL":null,"raw_pages":"81-5","medline_journal":"Nature","ISO_journal":"Nature","authors":["Ahel I","Ahel D","Matsusaka T","Clark AJ","Pines J","Boulton SJ","West SC."],"DOI_URL":"http://dx.doi.org/10.1038/nature06420"},"PUB00021744":{"PMID":12842467,"ISBN":null,"volume":"330","issue":"3","year":2003,"title":"The crystal structure of AF1521 a protein from Archaeoglobus fulgidus with homology to the non-histone domain of macroH2A.","URL":null,"raw_pages":"503-11","medline_journal":"J Mol Biol","ISO_journal":"J. Mol. Biol.","authors":["Allen MD","Buckle AM","Cordell SC","Lowe J","Bycroft M."],"DOI_URL":"http://dx.doi.org/10.1016/S0022-2836(03)00473-X"}},"set_info":{"accession":"CL0223","name":"MACRO"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":1119,"interactions":0,"matches":38291,"pathways":0,"proteins":32372,"proteomes":12852,"sets":1,"structural_models":{"alphafold":21017},"structures":1152,"taxa":24044},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":80,"alignment:full":24777},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"6lft","name":"Poa1p S30A mutant in complex with ADP-ribose"}}}