Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling

Journal article

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData availability: All collected atomic coordinates and structure factors have been deposited in the Protein Data Bank under accession codes 8RSI (MorMacro), 8RSJ (MorMacro:ADPr), 8RSK (MorMacro:Asn-ADPr), 8RSL (SauMacro), 8RSM (SpyMacro:ADPr), and 8RSN (Foc1Mfs1). SAXS profiles and pair distribution functions were uploaded to the SASBDB and are available under the accession codes SASDTX8 (lipoyl-SpyGcvH-L), SASDTY8 (SpyMacro), and SASDTZ8 (SpyMacro:lipoyl-SpyGcvH-L). Genomic sequences obtained in this study were deposited in GenBank under the accession numbers OR133610 (AteMfs1), OR133608 (Foc1Mfs1), OR133609 (PnpMfs1) and OR136504 (Foc1MacroD2).Dynamic ADP-ribosylation signalling is a crucial pathway that controls fundamental cellular processes, in particular, the response to cellular stresses such as DNA damage, reactive oxygen species and infection. In some pathogenic microbes the response to oxidative stress is controlled by a SirTM/zinc-containing macrodomain (Zn-Macro) pair responsible for establishment and removal of the modification, respectively. Targeting this defence mechanism against the host’s innate immune response may lead to novel approaches to support the fight against emerging antimicrobial resistance. Earlier studies suggested that Zn-Macros play a key role in the activation of this defence. Therefore, we used phylogenetic, biochemical, and structural approaches to elucidate the functional properties of these enzymes. Using the substrate mimetic asparagine-ADP-ribose as well as the ADP-ribose product, we characterise the catalytic role of the zinc ion in the removal of the ADP-ribosyl modification. Furthermore, we determined structural properties that contribute to substrate selectivity within the different Zn-Macro branches. Together, our data not only give new insights into the Zn-Macro family but also highlight their distinct features that may be exploited for the development of future therapies.Medical Research Council (MRC)China Scholarship Counci

Authors: Fontana, P; Buch-Larsen, SC; Suyari, O; Smith, R; Suskiewicz, MJ

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 14
• Issue: 1
• Pages: 3200-3200
• Publication date: 2023-06-02
• DOI: 10.1038/s41467-023-38793-y
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: NAD+ kinase; Biology; Serine; Cell biology; Drosophila (subgenus); Gene; Enzyme; Biochemistry; Phosphorylation; Computational biology; Signalling; Genetics; ADP-ribosylation