9R0S
human FAM118B pentameric filament
Summary for 9R0S
| Entry DOI | 10.2210/pdb9r0s/pdb |
| EMDB information | 53488 |
| Descriptor | Protein FAM118B (1 entity in total) |
| Functional Keywords | filament, enzyme, nad, nucleus, innate immunity, sirtuin, immune system |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 5 |
| Total formula weight | 208622.01 |
| Authors | Baretic, D.,Missoury, S.,Patel, K.,Coste, F.,Delarue, M.,Suskiewicz, J.M.,Ahel, I. (deposition date: 2025-04-24, release date: 2025-11-26, Last modification date: 2025-12-03) |
| Primary citation | Baretic, D.,Missoury, S.,Patel, K.,Martinez, M.,Coste, F.,Zhu, K.,Smith, R.,Kopasz, A.G.,Lu, Y.,Bigot, N.,Chapuis, C.,Riou, R.,Dukic, N.,Goffinont, S.,Pressoir, V.,Patacko, S.,Timinszky, G.,Delarue, M.,Castaing, B.,Ahel, D.,Mikoc, A.,Huet, S.,Ahel, I.,Suskiewicz, M.J. Filament formation and NAD processing by noncanonical human FAM118 sirtuins. Nat.Struct.Mol.Biol., 2025 Cited by PubMed Abstract: Sirtuins are an ancient family of enzymes with diverse nicotinamide adenine dinucleotide (NAD)-dependent activities. Here we identify family with sequence similarity 118 member B (FAM118B) and FAM118A-two understudied vertebrate proteins-as vertebrate-specific sirtuins with similarities to bacterial antiphage sirtuins. We show that human FAM118B forms head-to-tail filaments both in vitro and in living human cells, a feature that appears to be conserved in both FAM118B and its paralog FAM118A across vertebrates. While human FAM118B and FAM118A have individually very weak NAD-processing activity in vitro, their interaction leads to markedly increased activity, suggesting a tightly regulated system. The overexpression of wild-type human FAM118B and FAM118A leads to strongly decreased NAD levels in human cells, an effect that is abolished in catalytically dead or filament-deficient mutants. Our study highlights filament formation and NAD processing as conserved mechanisms among immunity-associated sirtuins across evolution. PubMed: 41249820DOI: 10.1038/s41594-025-01715-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5 Å) |
Structure validation
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