9R0P

human FAM118B trimeric filament

Summary for 9R0P

• Entry DOI: 10.2210/pdb9r0p/pdb
• EMDB information: 53487
• 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: 3
• Total formula weight: 125173.21

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: 2025-12-24)

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., 32:2526-2541, 2025

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: 41249820
DOI: 10.1038/s41594-025-01715-1

Experimental method

ELECTRON MICROSCOPY (4.1 Å)