9cmt
The crystal structure of HP1alpha CSD-Agno complex
Structural highlights
FunctionCBX5_HUMAN Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins.[1] Publication Abstract from PubMedChronically persistent viruses are integral components of the organismal ecosystem in humans and animals (1) (2) . Many of these viruses replicate and accumulate within the cell nucleus (3) . The nuclear location allows viruses to evade cytoplasmic host viral sensors and promotes viral replication (4) . 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 (5) , 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. Chromatin mimicry by human JC virus.,Schaefer U, Miroshnikova YA, Xie W, Larson AG, Lu Z, Chen S, Bradic M, Goldgur Y, Chen K, Sharma VP, Cao J, Patel DJ, Narlikar GJ, Wickstrom SA, Tarakhovsky A bioRxiv [Preprint]. 2024 Nov 4:2024.11.04.621823. doi: 10.1101/2024.11.04.621823. PMID:39803508[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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