Structural highlights
6n1z is a 6 chain structure with sequence from African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Gene: | IPO9, IMP9, KIAA1192, RANBP9, HSPC273 (HUMAN), hist1h2aj, LOC494591, XELAEV_18003602mg (African clawed frog) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[IPO9_HUMAN] Functions in nuclear protein import as nuclear transport receptor (PubMed:11823430). Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:11823430). 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 (PubMed:11823430). 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 (PubMed:11823430). 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 (PubMed:11823430). Mediates the nuclear import of RPS7, RPL18A, RPL6, histone H2A, histone H2B and histone (PubMed:11823430). Prevents the cytoplasmic aggregation of RPS7 and RPL18A by shielding exposed basic domains (PubMed:11823430). Mediates the nuclear import of actin (By similarity).[UniProtKB:Q91YE6][1] [H2B11_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Publication Abstract from PubMed
We report the crystal structure of nuclear import receptor Importin-9 bound to its cargo, the histones H2A-H2B. Importin-9 wraps around the core, globular region of H2A-H2B to form an extensive interface. The nature of this interface coupled with quantitative analysis of deletion mutants of H2A-H2B suggest that the NLS-like sequences in the H2A-H2B tails play a minor role in import. Importin-9*H2A-H2B is reminiscent of interactions between histones and histone chaperones in that it precludes H2A-H2B interactions with DNA and H3-H4 as seen in the nucleosome. Like many histone chaperones, which prevent inappropriate non-nucleosomal interactions, Importin-9 also sequesters H2A-H2B from DNA. Importin-9 appears to act as a storage chaperone for H2A-H2B while escorting it to the nucleus. Surprisingly, RanGTP does not dissociate Importin-9*H2A-H2B but assembles into a RanGTP*Importin-9*H2A-H2B complex. The presence of Ran in the complex, however, modulates Imp9-H2A-H2B interactions to facilitate its dissociation by DNA and assembly into a nucleosome.
Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone.,Padavannil A, Sarkar P, Kim SJ, Cagatay T, Jiou J, Brautigam CA, Tomchick DR, Sali A, D'Arcy S, Chook YM Elife. 2019 Mar 11;8. pii: 43630. doi: 10.7554/eLife.43630. PMID:30855230[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jakel S, Mingot JM, Schwarzmaier P, Hartmann E, Gorlich D. Importins fulfil a dual function as nuclear import receptors and cytoplasmic chaperones for exposed basic domains. EMBO J. 2002 Feb 1;21(3):377-86. doi: 10.1093/emboj/21.3.377. PMID:11823430 doi:http://dx.doi.org/10.1093/emboj/21.3.377
- ↑ Padavannil A, Sarkar P, Kim SJ, Cagatay T, Jiou J, Brautigam CA, Tomchick DR, Sali A, D'Arcy S, Chook YM. Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone. Elife. 2019 Mar 11;8. pii: 43630. doi: 10.7554/eLife.43630. PMID:30855230 doi:http://dx.doi.org/10.7554/eLife.43630
