11JG
Cryo-EM structure of pSTAT1 bound to importin alpha 5 (4:2 assembly)
This is a non-PDB format compatible entry.
Summary for 11JG
| Entry DOI | 10.2210/pdb11jg/pdb |
| Related | 11GR 11JG 11PH 38HT |
| EMDB information | 75683 75737 75922 78826 |
| Descriptor | Signal transducer and activator of transcription 1-alpha/beta, Importin subunit alpha-5 (2 entities in total) |
| Functional Keywords | importin, transcription factor, transport protein, nuclear protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 470637.28 |
| Authors | Kumar, P.,Bellis, N.F.,Yang, R.,Vinkemeier, U.,Cingolani, G. (deposition date: 2026-02-26, release date: 2026-11-04) |
| Primary citation | Kumar, P.,Cavey, J.R.,Yang, R.,White, O.,Begitt, A.,He, L.,Suinn, S.S.,Bellis, N.F.,Lokareddy, R.K.,Vinkemeier, U.,Cingolani, G. Cytokine-induced nuclear translocation of STAT1 via a non-transferable NLS. Biorxiv, 2026 Cited by PubMed Abstract: The targeting function of nuclear localization signals (NLSs) is generally considered independent of a protein's native sequence or fold and is readily transferable to heterologous cargos. Contrary to this paradigm, rapid nuclear translocation of phosphorylated STAT1 (pSTAT1) following cytokine stimulation requires importin β, Ran-GTP, and the importin α5 isoform, which recognizes a non-transferable NLS. Here, we present cryo-EM structures of pSTAT1 bound to importin α5, revealing an asymmetric 2:1 complex that diverges from canonical NLS-mediated cargo recognition. Importin α5 occupies the DNA-binding groove of the pSTAT1 dimer, with a single STAT1 N-terminal domain positioning the C-terminal Armadillo repeats 9-10 (S1B domain) orthogonal to the DNA-binding interface. This interface is also targeted by the Ebola virus protein VP24, an antagonist of interferon signaling. We further show that Ran-GTP alone is insufficient to trigger nuclear release of pSTAT1, which additionally requires the exportin CAS. A cryo-EM reconstruction of the CAS-Ran-GTP-α5 complex, supported by in vitro competition assays, demonstrates that CAS and pSTAT1 are mutually exclusive ligands for importin α5. Together, these findings define the molecular choreography of cytokine-induced STAT1 nuclear translocation and release, establishing a general paradigm for STAT family signaling. PubMed: 42856475DOI: 10.64898/2026.09.28.754937 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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