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Structure-based nuclear import mechanism of histones H3 and H4 mediated by Kap123.

An S, Yoon J, Kim H, Song JJ, Cho US
Elife 6 (2017)
Related entries: 5ve8, 5w0v

Cited: 11 times
EuropePMC logo PMID: 29035199

Abstract

Kap123, a major karyopherin protein of budding yeast, recognizes the nuclear localization signals (NLSs) of cytoplasmic histones H3 and H4 and translocates them into the nucleus during DNA replication. Mechanistic questions include H3- and H4-NLS redundancy toward Kap123 and the role of the conserved diacetylation of cytoplasmic H4 (K5ac and K12ac) in Kap123-mediated histone nuclear translocation. Here, we report crystal structures of full-length Kluyveromyces lactis Kap123 alone and in complex with H3- and H4-NLSs. Structures reveal the unique feature of Kap123 that possesses two discrete lysine-binding pockets for NLS recognition. Structural comparison illustrates that H3- and H4-NLSs share at least one of two lysine-binding pockets, suggesting that H3- and H4-NLSs are mutually exclusive. Additionally, acetylation of key lysine residues at NLS, particularly H4-NLS diacetylation, weakens the interaction with Kap123. These data support that cytoplasmic histone H4 diacetylation weakens the Kap123-H4-NLS interaction thereby facilitating histone Kap123-H3-dependent H3:H4/Asf1 complex nuclear translocation.

Articles - 5vch mentioned but not cited (1)

  1. Structure of IMPORTIN-4 bound to the H3-H4-ASF1 histone-histone chaperone complex. Bernardes NE, Fung HYJ, Li Y, Chen Z, Chook YM. Proc Natl Acad Sci U S A 119 e2207177119 (2022)


Reviews citing this publication (4)

  1. H3-H4 Histone Chaperone Pathways. Grover P, Asa JS, Campos EI. Annu Rev Genet 52 109-130 (2018)
  2. Karyopherins and condensates. Springhower CE, Rosen MK, Chook YM. Curr Opin Cell Biol 64 112-123 (2020)
  3. Recent insights into Histone Acetyltransferase-1: biological function and involvement in pathogenesis. Poziello A, Nebbioso A, Stunnenberg HG, Martens JHA, Carafa V, Altucci L. Epigenetics 16 838-850 (2021)
  4. Mechanisms of chromatin-based epigenetic inheritance. Du W, Shi G, Shan CM, Li Z, Zhu B, Jia S, Li Q, Zhang Z. Sci China Life Sci 65 2162-2190 (2022)

Articles citing this publication (6)

  1. PRMT5-mediated regulation of developmental myelination. Scaglione A, Patzig J, Liang J, Frawley R, Bok J, Mela A, Yattah C, Zhang J, Teo SX, Zhou T, Chen S, Bernstein E, Canoll P, Guccione E, Casaccia P. Nat Commun 9 2840 (2018)
  2. Evidence for the nuclear import of histones H3.1 and H4 as monomers. Apta-Smith MJ, Hernandez-Fernaud JR, Bowman AJ. EMBO J 37 (2018)
  3. Hat1 acetylates histone H4 and modulates the transcriptional program in Drosophila embryogenesis. Varga J, Korbai S, Neller A, Zsindely N, Bodai L. Sci Rep 9 17973 (2019)
  4. TFAM loss induces nuclear actin assembly upon mDia2 malonylation to promote liver cancer metastasis. Huang Q, Wu D, Zhao J, Yan Z, Chen L, Guo S, Wang D, Yuan C, Wang Y, Liu X, Xing J. EMBO J 41 e110324 (2022)
  5. Proteomic elucidation of the targets and primary functions of the picornavirus 2A protease. Serganov AA, Udi Y, Stein ME, Patel V, Fridy PC, Rice CM, Saeed M, Jacobs EY, Chait BT, Rout MP. J Biol Chem 298 101882 (2022)
  6. The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum. Poulet A, Rousselot E, Téletchéa S, Noirot C, Jacob Y, van Wolfswinkel J, Thiriet C, Duc C. Int J Mol Sci 24 1051 (2023)


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