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8f2q

From Proteopedia

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Human Parvovirus B19 Nonstructural NS1 Protein NLS bound to Importin Alpha 2

Structural highlights

8f2q is a 3 chain structure with sequence from Human parvovirus B19 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
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.

Publication Abstract from PubMed

Human parvovirus B19 (B19V) is a major human pathogen causing a variety of diseases, characterized by a selective tropism to human progenitor cells in bone marrow. In similar fashion to all Parvoviridae members, the B19V ssDNA genome is replicated within the nucleus of infected cells through a process which involves both cellular and viral proteins. Among the latter, a crucial role is played by non-structural protein (NS)1, a multifunctional protein involved in genome replication and transcription, as well as modulation of host gene expression and function. Despite the localization of NS1 within the host cell nucleus during infection, little is known regarding the mechanism of its nuclear transport pathway. In this study we undertake structural, biophysical, and cellular approaches to characterize this process. Quantitative confocal laser scanning microscopy (CLSM), gel mobility shift, fluorescence polarization and crystallographic analysis identified a short sequence of amino acids (GACHAKKPRIT-182) as the classical nuclear localization signal (cNLS) responsible for nuclear import, mediated in an energy and importin (IMP) alpha/beta-dependent fashion. Structure-guided mutagenesis of key residue K177 strongly impaired IMPalpha binding, nuclear import, and viral gene expression in a minigenome system. Further, treatment with ivermectin, an antiparasitic drug interfering with the IMPalpha/beta dependent nuclear import pathway, inhibited NS1 nuclear accumulation and viral replication in infected UT7/Epo-S1 cells. Thus, NS1 nuclear transport is a potential target of therapeutic intervention against B19V induced disease.

Importin alpha/beta-dependent nuclear transport of human parvovirus B19 nonstructural protein 1 is essential for viral replication.,Alvisi G, Manaresi E, Cross EM, Hoad M, Akbari N, Pavan S, Ariawan D, Bua G, Petersen GF, Forwood J, Gallinella G Antiviral Res. 2023 May;213:105588. doi: 10.1016/j.antiviral.2023.105588. Epub , 2023 Mar 28. PMID:36990397^[1]

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

References

↑ Alvisi G, Manaresi E, Cross EM, Hoad M, Akbari N, Pavan S, Ariawan D, Bua G, Petersen GF, Forwood J, Gallinella G. Importin α/β-dependent nuclear transport of human parvovirus B19 nonstructural protein 1 is essential for viral replication. Antiviral Res. 2023 May;213:105588. PMID:36990397 doi:10.1016/j.antiviral.2023.105588

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/8f2q"

Categories: Human parvovirus B19 | Large Structures | Mus musculus | Cross EM | Forwood JK

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8f2q]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_parvovirus_B19 Human parvovirus B19] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8F2Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F2Q 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=8f2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f2q OCA], [https://pdbe.org/8f2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f2q RCSB], [https://www.ebi.ac.uk/pdbsum/8f2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f2q 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]] 2.7&#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=8f2q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f2q OCA], [https://pdbe.org/8f2q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f2q RCSB], [https://www.ebi.ac.uk/pdbsum/8f2q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f2q ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 </div>
 <div class="pdbe-citations 8f2q" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Importin 3D structures|Importin 3D structures]]
 == References ==
 <references/>

8f2q

From Proteopedia

Current revision

Human Parvovirus B19 Nonstructural NS1 Protein NLS bound to Importin Alpha 2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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