5xbk | pdb_00005xbk
Crystal structure of human Importin4
Structural highlights
Function[IPO4_HUMAN] Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin 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 the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. 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 (By similarity). Mediates the nuclear import of RPS3A. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.[1] Publication Abstract from PubMedImportin4 transports histone H3/H4 in complex with Asf1a to the nucleus for chromatin assembly. Importin4 recognizes the nuclear localization sequence located at the N-terminal tail of histones. Here, we analyzed the structures and interactions of human Importin4, histones and Asf1a by cross-linking mass spectrometry (XL-MS), X-ray crystallography, negative-stain electron microscopy, small-angle X-ray scattering and integrative modeling. The XL-MS data showed that the C-terminal region of Importin4 was extensively crosslinked with the histone H3 tail. We determined the crystal structure of the C-terminal region of Importin4 bound to the histone H3 peptide, thus revealing that the acidic patch in Importin4 accommodates the histone H3 tail, and that histone H3 Lys14 contributes to the interaction with Importin4. In addition, we show that Asf1a modulates the binding of histone H3/H4 to Importin4. Furthermore, the molecular architecture of the Importin4_histone H3/H4_Asf1a complex was produced through an integrative modeling approach. Overall, this work provides structural insights into how Importin4 recognizes histones and their chaperone complex. Integrative structural investigation on the architecture of human Importin4_histone H3/H4_Asf1a complex and its histone H3 tail binding.,Yoon J, Kim SJ, An S, Cho S, Leitner A, Jung T, Aebersold R, Hebert H, Cho US, Song JJ J Mol Biol. 2018 Jan 30. pii: S0022-2836(18)30041-X. doi:, 10.1016/j.jmb.2018.01.015. PMID:29408485[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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