10sm: Difference between revisions

Latest revision as of 04:45, 27 May 2026

Importin-9 bound to ETS homologous factor (EHF)

Structural highlights

10sm is a 2 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:	Electron Microscopy, Resolution 3.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EHF_HUMAN Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Protein trafficking between the cytoplasm and the nucleus is a fundamental process in eukaryotic cell biology. While linear nuclear localization signals (NLSs) are well characterized, many nuclear proteins lack a predictable NLS. Here, we identify the ETS domain, a DNA-binding winged-helix fold, from ETS family transcription factors as a structure-encoded NLS. We show that ETS domains mediate nuclear import through direct nanomolar affinity recognition by IPO9. Cryo-electron microscopy analysis of the EHF:IPO9 complex reveals that the IPO9 wraps around the ETS domain and engages structural features throughout the winged-helix fold. Biochemical studies demonstrate that the ETS domain DNA-binding helix is critical for importin recognition and for NLS activity in mammalian cells. Comparison of IPO9 bound to EHF and the histone H2A:H2B dimer reveals distinct interaction hotspots, illustrating how IPO9 employs unique combinatorial binding surfaces to accommodate structurally diverse cargos. These findings define a unique class of globular NLSs and highlight the adaptability of importins in recognizing distinct protein folds.

Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.,McConville M, Lankford K, Bernardes NE, Walterscheid A, Valadez C, Niesman A, Chook YM, Liszczak G Proc Natl Acad Sci U S A. 2026 May 5;123(18):e2536763123. doi: , 10.1073/pnas.2536763123. Epub 2026 May 1. PMID:42066049^[6]

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

References

↑ Kleinbaum LA, Duggan C, Ferreira E, Coffey GP, Buttice G, Burton FH. Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF. Biochem Biophys Res Commun. 1999 Oct 14;264(1):119-26. doi: , 10.1006/bbrc.1999.1493. PMID:10527851 doi:https://dx.doi.org/10.1006/bbrc.1999.1493
↑ Kas K, Finger E, Grall F, Gu X, Akbarali Y, Boltax J, Weiss A, Oettgen P, Kapeller R, Libermann TA. ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. J Biol Chem. 2000 Jan 28;275(4):2986-98. doi: 10.1074/jbc.275.4.2986. PMID:10644770 doi:https://dx.doi.org/10.1074/jbc.275.4.2986
↑ Tugores A, Le J, Sorokina I, Snijders AJ, Duyao M, Reddy PS, Carlee L, Ronshaugen M, Mushegian A, Watanaskul T, Chu S, Buckler A, Emtage S, McCormick MK. The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades. J Biol Chem. 2001 Jun 8;276(23):20397-406. doi: 10.1074/jbc.M010930200. Epub 2001 , Mar 19. PMID:11259407 doi:https://dx.doi.org/10.1074/jbc.M010930200
↑ Silverman ES, Baron RM, Palmer LJ, Le L, Hallock A, Subramaniam V, Riese RJ, McKenna MD, Gu X, Libermann TA, Tugores A, Haley KJ, Shore S, Drazen JM, Weiss ST. Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. Am J Respir Cell Mol Biol. 2002 Dec;27(6):697-704. PMID:12444029 doi:10.1165/rcmb.2002-0011OC
↑ Lim JH, Cho JY, Park YB, Park JW, Kwon TK. ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites. Biochem Biophys Res Commun. 2006 Nov 24;350(3):736-41. PMID:17027647 doi:10.1016/j.bbrc.2006.09.102
↑ McConville M, Lankford K, Bernardes NE, Walterscheid A, Valadez C, Niesman A, Chook YM, Liszczak G. Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import. Proc Natl Acad Sci U S A. 2026 May 5;123(18):e2536763123. PMID:42066049 doi:10.1073/pnas.2536763123

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kleinbaum LA, Duggan C, Ferreira E, Coffey GP, Buttice G, Burton FH. Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF. Biochem Biophys Res Commun. 1999 Oct 14;264(1):119-26. doi: , 10.1006/bbrc.1999.1493. PMID:10527851 doi:https://dx.doi.org/10.1006/bbrc.1999.1493

[2] Kas K, Finger E, Grall F, Gu X, Akbarali Y, Boltax J, Weiss A, Oettgen P, Kapeller R, Libermann TA. ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. J Biol Chem. 2000 Jan 28;275(4):2986-98. doi: 10.1074/jbc.275.4.2986. PMID:10644770 doi:https://dx.doi.org/10.1074/jbc.275.4.2986

[3] Tugores A, Le J, Sorokina I, Snijders AJ, Duyao M, Reddy PS, Carlee L, Ronshaugen M, Mushegian A, Watanaskul T, Chu S, Buckler A, Emtage S, McCormick MK. The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades. J Biol Chem. 2001 Jun 8;276(23):20397-406. doi: 10.1074/jbc.M010930200. Epub 2001 , Mar 19. PMID:11259407 doi:https://dx.doi.org/10.1074/jbc.M010930200

[4] Silverman ES, Baron RM, Palmer LJ, Le L, Hallock A, Subramaniam V, Riese RJ, McKenna MD, Gu X, Libermann TA, Tugores A, Haley KJ, Shore S, Drazen JM, Weiss ST. Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung. Am J Respir Cell Mol Biol. 2002 Dec;27(6):697-704. PMID:12444029 doi:10.1165/rcmb.2002-0011OC

[5] Lim JH, Cho JY, Park YB, Park JW, Kwon TK. ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites. Biochem Biophys Res Commun. 2006 Nov 24;350(3):736-41. PMID:17027647 doi:10.1016/j.bbrc.2006.09.102

[6] McConville M, Lankford K, Bernardes NE, Walterscheid A, Valadez C, Niesman A, Chook YM, Liszczak G. Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import. Proc Natl Acad Sci U S A. 2026 May 5;123(18):e2536763123. PMID:42066049 doi:10.1073/pnas.2536763123

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[2]

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[6]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 10sm is ON HOLD  until Paper Publication
+==Importin-9 bound to ETS homologous factor (EHF)==
+<StructureSection load='10sm' size='340' side='right'caption='[[10sm]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[10sm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=10SM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=10SM FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=10sm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=10sm OCA], [https://pdbe.org/10sm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=10sm RCSB], [https://www.ebi.ac.uk/pdbsum/10sm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=10sm ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/EHF_HUMAN EHF_HUMAN] Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene.<ref>PMID:10527851</ref> <ref>PMID:10644770</ref> <ref>PMID:11259407</ref> <ref>PMID:12444029</ref> <ref>PMID:17027647</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Protein trafficking between the cytoplasm and the nucleus is a fundamental process in eukaryotic cell biology. While linear nuclear localization signals (NLSs) are well characterized, many nuclear proteins lack a predictable NLS. Here, we identify the ETS domain, a DNA-binding winged-helix fold, from ETS family transcription factors as a structure-encoded NLS. We show that ETS domains mediate nuclear import through direct nanomolar affinity recognition by IPO9. Cryo-electron microscopy analysis of the EHF:IPO9 complex reveals that the IPO9 wraps around the ETS domain and engages structural features throughout the winged-helix fold. Biochemical studies demonstrate that the ETS domain DNA-binding helix is critical for importin recognition and for NLS activity in mammalian cells. Comparison of IPO9 bound to EHF and the histone H2A:H2B dimer reveals distinct interaction hotspots, illustrating how IPO9 employs unique combinatorial binding surfaces to accommodate structurally diverse cargos. These findings define a unique class of globular NLSs and highlight the adaptability of importins in recognizing distinct protein folds.
-Authors: Bernardes, N.E., Lankford, K., McConville, M., Chook, Y.M., Liszczak, G.
+Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.,McConville M, Lankford K, Bernardes NE, Walterscheid A, Valadez C, Niesman A, Chook YM, Liszczak G Proc Natl Acad Sci U S A. 2026 May 5;123(18):e2536763123. doi: , 10.1073/pnas.2536763123. Epub 2026 May 1. PMID:42066049<ref>PMID:42066049</ref>
-Description: Importin-9 bound to ETS homologous factor (EHF)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chook, Y.M]]
+<div class="pdbe-citations 10sm" style="background-color:#fffaf0;"></div>
-[[Category: Lankford, K]]
+== References ==
-[[Category: Mcconville, M]]
+<references/>
-[[Category: Liszczak, G]]
+__TOC__
-[[Category: Bernardes, N.E]]
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bernardes NE]]
+[[Category: Chook YM]]
+[[Category: Lankford K]]
+[[Category: Liszczak G]]
+[[Category: McConville M]]

10sm: Difference between revisions

Latest revision as of 04:45, 27 May 2026

Importin-9 bound to ETS homologous factor (EHF)

Structural highlights

Function

Publication Abstract from PubMed

References

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