6n89 | pdb_00006n89
Cryo-EM structure of the Importin beta:Histone H1.0 complex
Structural highlights
Function[IMB1_HUMAN] Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor. Acting autonomously, serves itself as NLS receptor. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In association with IPO7 mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Imports PRKCI into the nucleus.[1] [2] [3] [H10_HUMAN] Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The H1F0 histones are found in cells that are in terminal stages of differentiation or that have low rates of cell division. Publication Abstract from PubMedProtein transport into the nucleus is mediated by transport receptors. Import of highly charged proteins, such as histone H1 and ribosomal proteins, requires a dimer of two transport receptors. In this study, we determined the cryo-EM structure of the Imp7:Impbeta:H1.0 complex, showing that the two importins form a cradle that accommodates the linker histone. The H1.0 globular domain is bound to Impbeta, whereas the acidic loops of Impbeta and Imp7 chaperone the positively charged C-terminal tail. Although it remains disordered, the H1 tail serves as a zipper that closes and stabilizes the structure through transient non-specific interactions with importins. Moreover, we found that the GGxxF and FxFG motifs in the Imp7 C-terminal tail are essential for Imp7:Impbeta dimerization and H1 import, resembling importin interaction with nucleoporins, which, in turn, promote complex disassembly. The architecture of many other complexes might be similarly defined by rapidly exchanging electrostatic interactions mediated by disordered regions. Fuzzy Interactions Form and Shape the Histone Transport Complex.,Ivic N, Potocnjak M, Solis-Mezarino V, Herzog F, Bilokapic S, Halic M Mol Cell. 2019 Feb 15. pii: S1097-2765(19)30052-8. doi:, 10.1016/j.molcel.2019.01.032. PMID:30824373[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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