9CMT

The crystal structure of HP1alpha CSD-Agno complex

Summary for 9CMT

• Entry DOI: 10.2210/pdb9cmt/pdb
• Descriptor: Chromobox protein homolog 5, Agnoprotein, 3',6'-DIHYDROXY-3-OXO-3H-SPIRO[2-BENZOFURAN-1,9'-XANTHENE]-5-CARBOXYLIC ACID (3 entities in total)
• Functional Keywords: heterochromatin protein 1 alpha, agnoprotein, jc polyomavirus, dimerization, viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 34054.70

Authors

Goldgur, Y.,Xie, W.,Schaefer, U.,Tarakhovsky, A.,Patel, D.,Chen, S. (deposition date: 2024-07-15, release date: 2025-05-28)

Primary citation

Schaefer, U.,Miroshnikova, Y.A.,Xie, W.,Larson, A.G.,Lu, Z.,Chen, S.,Bradic, M.,Goldgur, Y.,Chen, K.,Sharma, V.P.,Cao, J.,Patel, D.J.,Narlikar, G.J.,Wickstrom, S.A.,Tarakhovsky, A.
Chromatin mimicry by human JC virus.
Biorxiv, 2024

PubMed Abstract: Chronically persistent viruses are integral components of the organismal ecosystem in humans and animals . Many of these viruses replicate and accumulate within the cell nucleus . The nuclear location allows viruses to evade cytoplasmic host viral sensors and promotes viral replication . One of the unexplored and puzzling aspects of the viral nuclear lifecycle involves the virus's ability to deal with the physical constraints of nuclear architecture. To replicate and accumulate within the nucleus in large numbers sufficient for infection spreading, DNA viruses need to overcome the spatial limitations imposed by chromatin and the nuclear matrix. We found that one of the most widespread and potentially lethal human viruses, the JC polyomavirus , interferes with nuclear heterochromatin to create virus-occupied space. The JC virus's impact on heterochromatin is mediated by the viral nonstructural protein, Agnoprotein (Agno). Agno's interference with heterochromatin is governed by structurally diverse mimics of host epigenetic regulators that facilitate virus-induced chromatin reorganization and a dramatic decline in nuclear stiffness in the infected cells. The JCV epigenetic mimicry is critical for the virus infection, as evident from reduced replication of mimic-mutant viruses. Our data suggest that modulation of nuclear mechanical properties is a novel strategy enabling chronicity of the JC and possibly other nuclear virus infections.

PubMed: 39803508
DOI: 10.1101/2024.11.04.621823

Experimental method

X-RAY DIFFRACTION (3.17 Å)