Warning: Constant ABSPATH already defined in D:\www\www164\blog\wp-config.php on line 31 {"id":424,"date":"2022-04-23T14:33:10","date_gmt":"2022-04-23T12:33:10","guid":{"rendered":"https:\/\/www.protpi.ch\/blog\/?p=424"},"modified":"2022-02-22T12:28:24","modified_gmt":"2022-02-22T10:28:24","slug":"adp-ribosylation","status":"publish","type":"post","link":"https:\/\/www.protpi.ch\/blog\/bioinformatics\/2022\/04\/adp-ribosylation\/","title":{"rendered":"ADP-Ribosylation"},"content":{"rendered":"\n

ADP-ribosylation is a reversible post-translational modification in which one (mono-ADP-ribosylation) or multiple (poly-ADP-ribosylation) ADP-ribose moieties are attached onto a substrate protein by ADP ribosyltransferases.<\/p>\n\n\n\n

mono-ADP-Ribosylation<\/h2>\n\n\n\n

Overview<\/h3>\n\n\n\n

mono-ADP-ribosylation is a common post-translational modification, where an ADP-ribose moiety is transferred from NAD+<\/sup> to the substrate protein under the release of nicotinamide. The transfer of ADP-ribose occurs onto amino acid residues with a nucleophilic oxygen, nitrogen or sulfur.<\/p>\n\n\n\n

pKa<\/td>NC<\/td>Loss<\/td>Gain<\/td>Deltamass<\/td>H<\/td>AA<\/td>UV-Spec<\/td>Pattern<\/td><\/tr>
–<\/td>No<\/td>H<\/td>C15<\/sub>H22<\/sub>
N15<\/sub>O13<\/sub>P2<\/sub><\/td>		Av: 541.3011
M: 541.0611<\/td>		–<\/td>C, D, E,
K, N, Q,
R, S, T<\/td>		Yes*<\/td>–<\/td><\/tr><\/tbody><\/table>
Physicochemical properties of \u03b3-carboxylation that are stored in the modification database of Prot pi (NC: Native charge; H: Relative hydrophobicity; AA: Modified amino acid; Pattern: Regex for sequence-motif \u00a0recognition).

*Spectrum of ATP instead of ADP-ribose was taken since no spectrum of ADP-ribose was available. The major difference between the two molecules are the terminal phosphate\/ribose group. The absorbance in the UV-range however is mainly caused by the adenine moiety.<\/figcaption><\/figure>\n\n\n\n

In-depth mechanism<\/h3>\n\n\n\n

mono-ADP-ribosylation describes the process of attaching an ADP-ribose moiety directly onto an amino acid residue with nucleophilic oxygen, nitrogen or sulfur, forming an N-, O- or S-glycosidic bond. The donor of the ADP-moiety is nicotinamide adenine dinucleotide. The transfer is catalysed by various ADP-ribosyltransferasen. During the transfer, nicotinamide is released\u200b1\u20136\u200b<\/sup><\/span>. Primarily, arginine \u200b1\u20136\u200b<\/sup><\/span>, glutamate\u200b1\u20135\u200b<\/sup><\/span> and aspartate\u200b1\u20135\u200b<\/sup><\/span>, but to a lesser extent also asparagine\u200b1,2,5,6\u200b<\/sup><\/span>, lysine\u200b1\u20134\u200b<\/sup><\/span>, cysteine\u200b1,3,6\u200b<\/sup><\/span>, threonine\u200b3\u200b<\/sup><\/span>, glutamine\u200b6\u200b<\/sup><\/span> and histidine\u200b6\u200b<\/sup><\/span> residues have been described as acceptor for ADP-ribosylation. ADP-ribosylation increases the molecular mass of the modified protein by 541 Da\u200b2\u200b<\/sup><\/span>. Furthermore, an additional negative charge is introduced into the protein\u200b1\u200b<\/sup><\/span>. The mechanism of mono-ADP-ribosylation is shown in figure 1.<\/p>\n\n\n\n

\"\"
Figure 1: Mechanism of mono-ADP-ribosylation. An ADP-ribose moiety is transferred from nicotinamide adenine dinucleotide onto amino acid residues with a nucleophilic oxygen, nitrogen or sulfur. In the process nicotinamide is released. The reaction is catalysed by ADP-ribosyltransferases.<\/figcaption><\/figure>\n\n\n\n

It is assumed that mono-ADP-ribosylation was originally developed by bacteria as a defence mechanism against viruses, other bacterial species and antimicrobial molecules\u200b3\u200b<\/sup><\/span>. Otherwise not much is known about the functions of mono-ADP-ribosylation\u200b2\u200b<\/sup><\/span>.<\/p>\n\n\n\n

poly-ADP-ribosylation<\/h2>\n\n\n\n

Some ADP-ribosyltransferases are able to perform several ADP-ribosylations, which is called poly-ADP-ribosylation. In poly-ADP-ribosylation, further ADP-ribose moieties are added to the already protein-bound ADP-ribose, thus forming ADP-ribose polymers\u200b4,7\u200b<\/sup><\/span>. Chain elongation occurs via a nucleophilic attack of the C2″ hydroxyl of the adenine ribose on the C1″ of the next nicotinamide adenine dinucleotide\u200b4\u200b<\/sup><\/span>. The polymers may be irregularly branched, with a branching point every 20 – 60 units of linear ADP-ribose\u200b7\u200b<\/sup><\/span>. Since each ADP-ribose moiety adds a negative charge to the protein, a protein that previously was positively charged may no longer be charged or may even become negatively charged\u200b1\u200b<\/sup><\/span>. In contrast to mono-ADP-ribosylation, poly-ADP-ribosylation plays a crucial role in various major cellular and biological processes, such as DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses\u200b2,5\u200b<\/sup><\/span>.<\/p>\n\n\n\n

References<\/h3>
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    Simonet NG, Rasti G, Vaquero A. The Histone Code and Disease. In: Epigenetic Biomarkers and Diagnostics<\/i>. Elsevier; 2016:417-445. doi:10.1016\/b978-0-12-801899-6.00021-8<\/a><\/div>\n <\/div>\n<\/li>
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    Martello R, Leutert M, Jungmichel S, et al. Proteome-wide identification of the endogenous ADP-ribosylome of mammalian cells and tissue. Nat Commun<\/i>. Published online September 30, 2016. doi:10.1038\/ncomms12917<\/a><\/div>\n <\/div>\n<\/li>
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    Cohen MS, Chang P. Insights into the biogenesis, function, and regulation of ADP-ribosylation. Nat Chem Biol<\/i>. Published online February 14, 2018:236-243. doi:10.1038\/nchembio.2568<\/a><\/div>\n <\/div>\n<\/li>
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    L\u00fcscher B, B\u00fctepage M, Eckei L, Krieg S, Verheugd P, Shilton BH. ADP-Ribosylation, a Multifaceted Posttranslational Modification Involved in the Control of Cell Physiology in Health and Disease. Chem Rev<\/i>. Published online November 27, 2017:1092-1136. doi:10.1021\/acs.chemrev.7b00122<\/a><\/div>\n <\/div>\n<\/li>
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    Palazzo L, Mikol\u010devi\u0107 P, Miko\u010d A, Ahel I. ADP-ribosylation signalling and human disease. Open Biol<\/i>. Published online April 2019:190041. doi:10.1098\/rsob.190041<\/a><\/div>\n <\/div>\n<\/li>
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    Green KD, Garneau-Tsodikova S. Posttranslational Modification of Proteins. In: Comprehensive Natural Products II<\/i>. Elsevier; 2010:433-468. doi:10.1016\/b978-008045382-8.00662-6<\/a><\/div>\n <\/div>\n<\/li>
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    Hassa P O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci<\/i>. Published online 2008:3046. doi:10.2741\/2909<\/a><\/div>\n <\/div>\n<\/li><\/ol><\/section>\n","protected":false},"excerpt":{"rendered":"

    ADP-ribosylation is a reversible post-translational modification in which one (mono-ADP-ribosylation) or multiple (poly-ADP-ribosylation) ADP-ribose moieties are attached onto a substrate protein by ADP ribosyltransferases. mono-ADP-Ribosylation Overview mono-ADP-ribosylation is a common post-translational modification, where an ADP-ribose moiety is transferred from NAD+ to the substrate protein under the release of nicotinamide. The transfer of ADP-ribose occurs onto […]<\/p>\n","protected":false},"author":11,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[51,45,44,57],"class_list":["post-424","post","type-post","status-publish","format-standard","hentry","category-bioinformatics","tag-glycosidic-bond","tag-marylation","tag-parylation","tag-post-translational-modification"],"jetpack_featured_media_url":"","_links":{"self":[{"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/posts\/424","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/users\/11"}],"replies":[{"embeddable":true,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/comments?post=424"}],"version-history":[{"count":14,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/posts\/424\/revisions"}],"predecessor-version":[{"id":512,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/posts\/424\/revisions\/512"}],"wp:attachment":[{"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/media?parent=424"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/categories?post=424"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.protpi.ch\/blog\/wp-json\/wp\/v2\/tags?post=424"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}