8P0C
Rubella virus p150 macro domain (apo)
Summary for 8P0C
| Entry DOI | 10.2210/pdb8p0c/pdb |
| Descriptor | Non-structural polyprotein p200 (2 entities in total) |
| Functional Keywords | macro domain, a1pp domain, adp-ribosylhydrolase, adp-ribose, hydrolase |
| Biological source | Rubella virus |
| Total number of polymer chains | 2 |
| Total formula weight | 39901.65 |
| Authors | Stoll, G.A.,Modis, Y. (deposition date: 2023-05-10, release date: 2024-01-17, Last modification date: 2024-03-06) |
| Primary citation | Stoll, G.A.,Nikolopoulos, N.,Zhai, H.,Zhang, L.,Douse, C.H.,Modis, Y. Crystal structure and biochemical activity of the macrodomain from rubella virus p150. J.Virol., 98:e0177723-e0177723, 2024 Cited by PubMed Abstract: Rubella virus encodes a nonstructural polyprotein with RNA polymerase, methyltransferase, and papain-like cysteine protease activities, along with a putative macrodomain of unknown function. Macrodomains bind ADP-ribose adducts, a post-translational modification that plays a key role in host-virus conflicts. Some macrodomains can also remove the mono-ADP-ribose adduct or degrade poly-ADP-ribose chains. Here, we report high-resolution crystal structures of the macrodomain from rubella virus nonstructural protein p150, with and without ADP-ribose binding. The overall fold is most similar to macroD-type macrodomains from various nonviral species. The specific composition and structure of the residues that coordinate ADP-ribose in the rubella virus macrodomain are most similar to those of macrodomains from alphaviruses. Isothermal calorimetry shows that the rubella virus macrodomain binds ADP-ribose in solution. Enzyme assays show that the rubella virus macrodomain can hydrolyze both mono- and poly-ADP-ribose adducts. Site-directed mutagenesis identifies Asn39 and Cys49 required for mono-ADP-ribosylhydrolase (de-MARylation) activity.IMPORTANCERubella virus remains a global health threat. Rubella infections during pregnancy can cause serious congenital pathology, for which no antiviral treatments are available. Our work demonstrates that, like alpha- and coronaviruses, rubiviruses encode a mono-ADP-ribosylhydrolase with a structurally conserved macrodomain fold to counteract MARylation by poly (ADP-ribose) polymerases (PARPs) in the host innate immune response. Our structural data will guide future efforts to develop novel antiviral therapeutics against rubella or infections with related viruses. PubMed: 38289106DOI: 10.1128/jvi.01777-23 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.72 Å) |
Structure validation
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