7unk

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Structure of Importin-4 bound to the H3-H4-ASF1 histone-histone chaperone complex

Structural highlights

7unk is a 4 chain structure with sequence from Homo sapiens, Saccharomyces cerevisiae and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.45Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

IMPORTIN-4, the primary nuclear import receptor of core histones H3 and H4, binds the H3-H4 dimer and histone chaperone ASF1 prior to nuclear import. However, how H3-H3-ASF1 is recognized for transport cannot be explained by available crystal structures of IMPORTIN-4-histone tail peptide complexes. Our 3.5-A IMPORTIN-4-H3-H4-ASF1 cryoelectron microscopy structure reveals the full nuclear import complex and shows a binding mode different from suggested by previous structures. The N-terminal half of IMPORTIN-4 clamps the globular H3-H4 domain and H3 alphaN helix, while its C-terminal half binds the H3 N-terminal tail weakly; tail contribution to binding energy is negligible. ASF1 binds H3-H4 without contacting IMPORTIN-4. Together, ASF1 and IMPORTIN-4 shield nucleosomal H3-H4 surfaces to chaperone and import it into the nucleus where RanGTP binds IMPORTIN-4, causing large conformational changes to release H3-H4-ASF1. This work explains how full-length H3-H4 binds IMPORTIN-4 in the cytoplasm and how it is released in the nucleus.

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. 2022 Sep 20;119(38):e2207177119. doi: , 10.1073/pnas.2207177119. Epub 2022 Sep 14. PMID:36103578[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
2 reviews cite this structure
Nuclear transport proteins: structure, function, and disease relevance.
Yang et al. (2023)
1 more
5 other articles
No citations found

See Also

References

  1. ↑ 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
  2. ↑ Bernardes NE, Fung HYJ, Li Y, Chen Z, Chook YM. Structure of IMPORTIN-4 bound to the H3-H4-ASF1 histone-histone chaperone complex. Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2207177119. PMID:36103578 doi:10.1073/pnas.2207177119

Contents


PDB ID 7unk

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OCA

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