7cru

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hnRNPK NLS in complex with Importin alpha 1 (KPNA2)

Structural highlights

7cru is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:ACT, GOL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HNRPK_HUMAN One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest.[1] [2] [3]

Publication Abstract from PubMed

The majority of lncRNAs and a small fraction of mRNAs localize in the cell nucleus to exert their functions. A SIRLOIN RNA motif was previously reported to drive its nuclear localization by the RNA-binding protein hnRNPK. However, the underlying mechanism remains unclear. Here, we report crystal structures of hnRNPK in complex with SIRLOIN, and with the nuclear import receptor (NIR) Impalpha1, respectively. The protein hnRNPK bound to SIRLOIN with multiple weak interactions, and interacted Impalpha1 using an independent high-affinity site. Forming a complex with hnRNPK and Impalpha1 was essential for the nuclear import and stress granule localization of SIRLOIN in semi-permeabilized cells. Nuclear import of SIRLOIN enhanced with increasing NIR concentrations, but its stress granule localization peaked at a low NIR concentration. Collectively, we propose a mechanism of SIRLOIN localization, in which NIRs functioned as drivers/regulators, and hnRNPK as an adaptor.

Nuclear import receptors and hnRNPK mediates nuclear import and stress granule localization of SIRLOIN.,Yao J, Tu Y, Shen C, Zhou Q, Xiao H, Jia D, Sun Q Cell Mol Life Sci. 2021 Dec;78(23):7617-7633. doi: 10.1007/s00018-021-03992-7. , Epub 2021 Oct 23. PMID:34689235[4]

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

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Citations
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Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats.
D'Souza et al. (2022)
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See Also

References

  1. ↑ Moumen A, Masterson P, O'Connor MJ, Jackson SP. hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell. 2005 Dec 16;123(6):1065-78. PMID:16360036 doi:http://dx.doi.org/10.1016/j.cell.2005.09.032
  2. ↑ Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010 Aug 6;142(3):409-19. doi: 10.1016/j.cell.2010.06.040. PMID:20673990 doi:10.1016/j.cell.2010.06.040
  3. ↑ Pelisch F, Pozzi B, Risso G, Munoz MJ, Srebrow A. DNA damage-induced heterogeneous nuclear ribonucleoprotein K sumoylation regulates p53 transcriptional activation. J Biol Chem. 2012 Aug 31;287(36):30789-99. doi: 10.1074/jbc.M112.390120. Epub, 2012 Jul 23. PMID:22825850 doi:http://dx.doi.org/10.1074/jbc.M112.390120
  4. ↑ Yao J, Tu Y, Shen C, Zhou Q, Xiao H, Jia D, Sun Q. Nuclear import receptors and hnRNPK mediates nuclear import and stress granule localization of SIRLOIN. Cell Mol Life Sci. 2021 Dec;78(23):7617-7633. PMID:34689235 doi:10.1007/s00018-021-03992-7

Contents


PDB ID 7cru

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OCA

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