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7lf4

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Structure of importin a3 bound to the p50- and p65-NLSs

Structural highlights

7lf4 is a 6 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 2.85Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IMA3_HUMAN Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

Publication Abstract from PubMed

Nuclear translocation of the p50/p65 heterodimer is essential for NF-kappaB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IkappaBalpha in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin alpha3 and the receptor importin beta. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin alpha3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin alpha3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin alpha1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for alpha3. We propose that importin alpha3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-kappaB signaling.

Differential recognition of canonical NF-kappaB dimers by Importin alpha3.,Florio TJ, Lokareddy RK, Yeggoni DP, Sankhala RS, Ott CA, Gillilan RE, Cingolani G Nat Commun. 2022 Mar 8;13(1):1207. doi: 10.1038/s41467-022-28846-z. PMID:35260573^[1]

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

References

↑ Florio TJ, Lokareddy RK, Yeggoni DP, Sankhala RS, Ott CA, Gillilan RE, Cingolani G. Differential recognition of canonical NF-kappaB dimers by Importin alpha3. Nat Commun. 2022 Mar 8;13(1):1207. doi: 10.1038/s41467-022-28846-z. PMID:35260573 doi:http://dx.doi.org/10.1038/s41467-022-28846-z

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7lf4"

Categories: Homo sapiens | Large Structures | Cingolani G | Florio TJ | Lokareddy RK

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7lf4]] is a 6 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=7LF4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LF4 FirstGlance]. <br>
-</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=7lf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lf4 OCA], [https://pdbe.org/7lf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lf4 RCSB], [https://www.ebi.ac.uk/pdbsum/7lf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lf4 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#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=7lf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lf4 OCA], [https://pdbe.org/7lf4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lf4 RCSB], [https://www.ebi.ac.uk/pdbsum/7lf4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lf4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 7lf4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Importin 3D structures|Importin 3D structures]]
 == References ==
 <references/>

7lf4

From Proteopedia

Current revision

Structure of importin a3 bound to the p50- and p65-NLSs

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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