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4zdu

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Revision as of 07:05, 19 June 2019

Crystal structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein

Structural highlights

4zdu is a 2 chain structure with sequence from I34a1 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Kpna2, Rch1 (LK3 transgenic mice), NP (I34A1)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IMA1_MOUSE] 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. [NCAP_I34A1] Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus.

Publication Abstract from PubMed

A non-classical nuclear localization signal (ncNLS) of influenza A virus nucleoprotein (NP) is critical for nuclear import of viral genomic RNAs that transcribe and replicate in the nucleus of infected cells. Here we report a 2.3 A resolution crystal structure of mouse importin-alpha1 in complex with NP ncNLS. The structure reveals that NP ncNLS binds specifically and exclusively to the minor NLS-binding site of importin-alpha. Structural and functional analyses identify key binding pockets on importin-alpha as potential targets for antiviral drug development. Unlike many other NLSs, NP ncNLS binds to the NLS-binding domain of importin-alpha weakly with micromolar affinity. These results suggest that a modest inhibitor with low affinity to importin-alpha could have anti-influenza activity with minimal cytotoxicity.

Structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein.,Nakada R, Hirano H, Matsuura Y Sci Rep. 2015 Oct 12;5:15055. doi: 10.1038/srep15055. PMID:26456934^[1]

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

References

↑ Nakada R, Hirano H, Matsuura Y. Structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein. Sci Rep. 2015 Oct 12;5:15055. doi: 10.1038/srep15055. PMID:26456934 doi:http://dx.doi.org/10.1038/srep15055

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/4zdu"

@@ Line 1: / Line 1: @@
 ==Crystal structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein==
-<StructureSection load='4zdu' size='340' side='right' caption='[[4zdu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='4zdu' size='340' side='right'caption='[[4zdu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4zdu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZDU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4zdu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/I34a1 I34a1] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZDU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZDU FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdu OCA], [http://pdbe.org/4zdu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zdu RCSB], [http://www.ebi.ac.uk/pdbsum/4zdu PDBsum]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2, Rch1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), NP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=211044 I34A1])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zdu OCA], [http://pdbe.org/4zdu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zdu RCSB], [http://www.ebi.ac.uk/pdbsum/4zdu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zdu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 18: @@
 </div>
 <div class="pdbe-citations 4zdu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Importin|Importin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: I34a1]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Hirano, H]]
 [[Category: Matsuura, Y]]

4zdu

From Proteopedia

Revision as of 07:05, 19 June 2019

Crystal structure of importin-alpha bound to a non-classical nuclear localization signal of the influenza A virus nucleoprotein

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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