Cryo-EM structure of human full-length XPO1 (unliganded)

2025-12-03 REL RCSB INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY INITIAL_RELEASE REPOSITORY DATABASE_REFERENCES citation citation_author em_admin _citation.country _citation.journal_abbrev _citation.journal_id_CSD _citation.journal_id_ISSN _citation.pdbx_database_id_DOI _citation.pdbx_database_id_PubMed _citation.title _citation.year _em_admin.last_update RCSB RCSB 2025-04-30 2025-11-26 2025-11-26 2025-12-03 Cancer Prevention and Research Institute of Texas (CPRIT) RP220582 United States Cancer Prevention and Research Institute of Texas (CPRIT) RP180410 United States Cancer Prevention and Research Institute of Texas (CPRIT) RP150053 United States Cancer Prevention and Research Institute of Texas (CPRIT) RP170170 United States National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) R35GM144137 United States National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) T32GM131963 United States Welch Foundation I-1532 United States Cryo-EM structure of human full-length XPO1 (unliganded) Wing CE Fung HYJ Chook YM nuclear export, HEAT repeat, PROTEIN TRANSPORT Wing CE Fung HYJ Kwanten B Cagatay T Niesman AB Jacquemyn M Gharghabi M Permentier B Shakya B Nandi R Ready JM Kashyap T Shacham S Landesman Y Lapalombella R Daelemans D Chook YM SINE compounds activate exportin-1 degradation via an allosteric mechanism. Biorxiv US 2025 39416201 doi:10.1101/2024.10.07.617049 2692-8205 9og9 FULLOVERLAP EMDB EMD-70458 associated EM volume

Human full-length unliganded exportin-1 (XPO1) Human full-length unliganded exportin-1 (XPO1) 0 1 Homo sapiens 0.123 Exportin-1 Homo sapiens 0.12366248399999999

GS remaining after TEV cleavage

1 Escherichia coli BL21(DE3) LEVO GSMPAIMTMLADHAARQLLDFSQKLDINLLDNVVNCLYHGEGAQQRMAQEVLTHLKEHPDAWTRVDTILEFSQNMNTKYY GLQILENVIKTRWKILPRNQCEGIKKYVVGLIIKTSSDPTCVEKEKVYIGKLNMILVQILKQEWPKHWPTFISDIVGASR TSESLCQNNMVILKLLSEEVFDFSSGQITQVKSKHLKDSMCNEFSQIFQLCQFVMENSQNAPLVHATLETLLRFLNWIPL GYIFETKLISTLIYKFLNVPMFRNVSLKCLTEIAGVSVSQYEEQFVTLFTLTMMQLKQMLPLNTNIRLAYSNGKDDEQNF IQNLSLFLCTFLKEHDQLIEKRLNLRETLMEALHYMLLVSEVEETEIFKICLEYWNHLAAELYRESPFSTSASPLLSGSQ HFDVPPRRQLYLPMLFKVRLLMVSRMAKPEEVLVVENDQGEVVREFMKDTDSINLYKNMRETLVYLTHLDYVDTERIMTE KLHNQVNGTEWSWKNLNTLCWAIGSISGAMHEEDEKRFLVTVIKDLLGLCEQKRGKDNKAIIASNIMYIVGQYPRFLRAH WKFLKTVVNKLFEFMHETHDGVQDMACDTFIKIAQKCRRHFVQVQVGEVMPFIDEILNNINTIICDLQPQQVHTFYEAVG YMIGAQTDQTVQEHLIEKYMLLPNQVWDSIIQQATKNVDILKDPETVKQLGSILKTNVRACKAVGHPFVIQLGRIYLDML NVYKCLSENISAAIQANGEMVTKQPLIRSMRTVKRETLKLISGWVSRSNDPQMVAENFVPPLLDAVLIDYQRNVPAAREP EVLSTMAIIVNKLGGHITAEIPQIFDAVFECTLNMINKDFEEYPEHRTNFFLLLQAVNSHCFPAFLAIPPTQFKLVLDSI IWAFKHTMRNVADTGLQILFTLLQNVAQEEAAAQSFYQTYFCDILQHIFSVVTDTSHTAGLTMHASILAYMFNLVEEGKI STSLNPGNPVNNQIFLQEYVANLLKSAFPHLQDAQVKLFVTGLFSLNQDIPAFKEHLRDFLVQIKEFAGEDTSDLFLEER EIALRQADEEKHKRQMSVPGIFNPHEIPEEMCD O14980 singleParticle particle 3.4 7.4

20 mM HEPES pH 7.4, 110 mM KOAc, 2 mM Mg(OAc)2, 2 mM TCEP

Quantifoil R1.2/1.3 COPPER 300 GLOW DISCHARGE 80 ETHANE 95 377 FEI VITROBOT MARK IV TFS KRIOS FLOOD BEAM BRIGHT FIELD FIELD EMISSION GUN 300 0.9 2.2 165000.0 FEI TITAN KRIOS AUTOGRID HOLDER TFS Selectris X 10 FEI FALCON IV (4k x 4k) 1 8568 60.0 1 1245354

blob picking followed by Topaz picking

cryoSPARC PHASE FLIPPING AND AMPLITUDE CORRECTION

Ab initio

2.93 FSC 0.143 CUT-OFF cryoSPARC 365756 MAXIMUM LIKELIHOOD cryoSPARC MAXIMUM LIKELIHOOD cryoSPARC emd_70458.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 330 330 330 0 0 0 330 330 330 243.54 243.54 243.54 90.0 90.0 90.0 X Y Z -0.16548671 0.36378536 0.0011256612 0.009287747 0.738 0.738 0.738 0.0808 AUTHOR ::::EMDATABANK.org::::EMD-70458:::: 3GB8 A PDB experimental model OTHER

Initial model was docked into maps using UCSF ChimeraX then manually built using Isolde and Coot and refined in PHENIX

REAL 124.049999999999997 emd_70458_half_map_2.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 330 330 330 0 0 0 330 330 330 243.54 243.54 243.54 90.0 90.0 90.0 X Y Z -0.17933635 0.4171081 0.00076834304 0.017230492 0.738 0.738 0.738 AUTHOR ::::EMDATABANK.org::::EMD-70458:::: emd_70458_half_map_1.map.gz 1 IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) 330 330 330 0 0 0 330 330 330 243.54 243.54 243.54 90.0 90.0 90.0 X Y Z -0.182497 0.41130438 0.00076404656 0.0172493 0.738 0.738 0.738 AUTHOR ::::EMDATABANK.org::::EMD-70458::::