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Structural basis for importin alpha 3 specificity of W proteins in Hendra and Nipah viruses.

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Smith KM, Tsimbalyuk S, Edwards MR, Cross EM, Batra J, Soares da Costa TP, Aragão D, Basler CF, Forwood JK
OpenAccess logo Nat Commun 9 3703 (2018)
Related entries: 6bvt, 6bvv, 6bvz, 6bw0, 6bw1, 6bwa, 6bwb

Cited: 36 times
EuropePMC logo PMID: 30209309

Abstract

Seven human isoforms of importin α mediate nuclear import of cargo in a tissue- and isoform-specific manner. How nuclear import adaptors differentially interact with cargo harbouring the same nuclear localisation signal (NLS) remains poorly understood, as the NLS recognition region is highly conserved. Here, we provide a structural basis for the nuclear import specificity of W proteins in Hendra and Nipah viruses. We determine the structural interfaces of these cargo bound to importin α1 and α3, identifying a 2.4-fold more extensive interface and > 50-fold higher binding affinity for importin α3. Through the design of importin α1 and α3 chimeric and mutant proteins, together with structures of cargo-free importin α1 and α3 isoforms, we establish that the molecular basis of specificity resides in the differential positioning of the armadillo repeats 7 and 8. Overall, our study provides mechanistic insights into a range of important nucleocytoplasmic transport processes reliant on isoform adaptor specificity.

Articles - 6bw9 mentioned but not cited (4)

  1. Structural basis for nuclear import selectivity of pioneer transcription factor SOX2. Jagga B, Edwards M, Pagin M, Wagstaff KM, Aragão D, Roman N, Nanson JD, Raidal SR, Dominado N, Stewart M, Jans DA, Hime GR, Nicolis SK, Basler CF, Forwood JK. Nat Commun 12 28 (2021)
  2. A novel likely pathogenic variant in the FBXO32 gene associated with dilated cardiomyopathy according to whole‑exome sequencing. Ghasemi S, Mahdavi M, Maleki M, Salahshourifar I, Kalayinia S. BMC Med Genomics 15 234 (2022)
  3. Structural characterization of human importin alpha 7 in its cargo-free form at 2.5 Å resolution. Tsimbalyuk S, Donnelly CM, Forwood JK. Sci Rep 12 315 (2022)
  4. Crystallographic data of an importin-α3 dimer in which the two protomers are bridged by a bipartite nuclear localization signal. Matsuura Y. Data Brief 47 108988 (2023)


Reviews citing this publication (9)

  1. Karyopherin-mediated nucleocytoplasmic transport. Wing CE, Fung HYJ, Chook YM. Nat Rev Mol Cell Biol 23 307-328 (2022)
  2. Antivirals that target the host IMPα/β1-virus interface. Martin AJ, Jans DA. Biochem Soc Trans 49 281-295 (2021)
  3. Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene. Douglas J, Drummond AJ, Kingston RL. Virus Evol 7 veab028 (2021)
  4. Nuclear-Import Receptors Counter Deleterious Phase Transitions in Neurodegenerative Disease. Odeh HM, Fare CM, Shorter J. J Mol Biol 434 167220 (2022)
  5. The Intrinsically Disordered W Protein Is Multifunctional during Henipavirus Infection, Disrupting Host Signalling Pathways and Nuclear Import. Tsimbalyuk S, Cross EM, Hoad M, Donnelly CM, Roby JA, Forwood JK. Cells 9 E1913 (2020)
  6. Nucleus-Targeting Phototherapy Nanodrugs for High-Effective Anti-Cancer Treatment. Long X, Zhang X, Chen Q, Liu M, Xiang Y, Yang Y, Xiao Z, Huang J, Wang X, Liu C, Nan Y, Huang Q. Front Pharmacol 13 905375 (2022)
  7. Nuclear transport proteins: structure, function, and disease relevance. Yang Y, Guo L, Chen L, Gong B, Jia D, Sun Q. Signal Transduct Target Ther 8 425 (2023)
  8. Are we ready to fight the Nipah virus pandemic? An overview of drug targets, current medications, and potential leads. Yang S, Kar S. Struct Chem 1-19 (2023)
  9. Viral Targeting of Importin Alpha-Mediated Nuclear Import to Block Innate Immunity. Vogel OA, Forwood JK, Leung DW, Amarasinghe GK, Basler CF. Cells 13 71 (2023)

Articles citing this publication (23)



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