9TNZ

SP100 CARD filament

This is a non-PDB format compatible entry.

Summary for 9TNZ

• Entry DOI: 10.2210/pdb9tnz/pdb
• EMDB information: 56096
• Descriptor: Maltose/maltodextrin-binding periplasmic protein,Nuclear autoantigen Sp-100 (1 entity in total)
• Functional Keywords: innate immunity, interferon, dna damage, cryo-em, immune system
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 26
• Total formula weight: 1530728.37

Authors

Rabl, J.,Aird, E.,Corn, J. (deposition date: 2025-12-16, release date: 2026-02-11, Last modification date: 2026-04-29)

Primary citation

Aird, E.J.,Rabl, J.,Knuesel, T.,Groen, K.,Awwad, S.W.,Korablev, B.,Scherpe, L.,Al-Herz, W.,Hupfer, R.,Recher, M.,Jackson, S.P.,Hale, B.G.,Corn, J.E.
An SP110-SP100 axis is a critical regulator of promyelocytic leukaemia body dynamics and mitotic fidelity.
Nat.Cell Biol., 28:684-695, 2026

PubMed Abstract: Stimulation of the innate immune system by foreign RNA elicits a potent interferon response and can trigger cell death. The mechanisms by which cells balance a robust response with cell-intrinsic lethality are still being uncovered. Here, using genome-wide CRISPR-Cas9 genetic screens with triphosphorylated RNA stimulation, we discover that promyelocytic leukaemia (PML) nuclear body-localized speckled protein 110 (SP110) is a potent inhibitor of type 1 interferon-driven cell death. Death suppression by SP110 counteracts a toxic activity of SP100, a major constituent of PML bodies. Loss of SP110 leads to mitotic retention of SP100 and PML bodies, which associate with and perturb segregating chromosomes, leading to micronucleus formation, DNA damage and genotoxic cell death. A combination of cryo-electron microscopy, AlphaFold modelling and cellular biochemistry reveals that SP110 dissolves toxic SP100 oligomers via necessary and sufficient direct interactions between their caspase activation and recruitment domains. These data reveal the critical roles of SP100 and SP110 in governing the disassembly of PML bodies during mitosis, as well as the repercussions if this process is misregulated.

PubMed: 41826696
DOI: 10.1038/s41556-026-01916-w

Experimental method

ELECTRON MICROSCOPY (3.52 Å)