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{{STRUCTURE_3tpm| PDB=3tpm | SCENE= }}
==Crystal structure of MAL RPEL domain in complex with importin-alpha==
===Crystal structure of MAL RPEL domain in complex with importin-alpha===
<StructureSection load='3tpm' size='340' side='right' caption='[[3tpm]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
{{ABSTRACT_PUBMED_21964294}}
== Structural highlights ==
<table><tr><td colspan='2'>[[3tpm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TPM FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tpo|3tpo]], [[3tpq|3tpq]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kpna2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Mkl1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=3tpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tpm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tpm RCSB], [http://www.ebi.ac.uk/pdbsum/3tpm PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin alpha/beta heterodimer, and that G-actin competes with importin alpha/beta for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-alpha, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-alpha- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-alpha recognition.


==Function==
Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.,Hirano H, Matsuura Y Biochem Biophys Res Commun. 2011 Oct 22;414(2):373-8. doi:, 10.1016/j.bbrc.2011.09.079. Epub 2011 Sep 21. PMID:21964294<ref>PMID:21964294</ref>
[[http://www.uniprot.org/uniprot/IMA2_MOUSE IMA2_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.  


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[3tpm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TPM OCA].
</div>


==Reference==
==See Also==
<ref group="xtra">PMID:021964294</ref><references group="xtra"/><references/>
*[[Importin|Importin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Hirano, H.]]
[[Category: Hirano, H]]
[[Category: Matsuura, Y.]]
[[Category: Matsuura, Y]]
[[Category: Nuclear import]]
[[Category: Nuclear import]]
[[Category: Protein transport-transcription complex]]
[[Category: Protein transport-transcription complex]]

Revision as of 09:48, 21 December 2014

Crystal structure of MAL RPEL domain in complex with importin-alphaCrystal structure of MAL RPEL domain in complex with importin-alpha

Structural highlights

3tpm is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:Kpna2 (Mus musculus), Mkl1 (Mus musculus)
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin alpha/beta heterodimer, and that G-actin competes with importin alpha/beta for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-alpha, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-alpha- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-alpha recognition.

Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.,Hirano H, Matsuura Y Biochem Biophys Res Commun. 2011 Oct 22;414(2):373-8. doi:, 10.1016/j.bbrc.2011.09.079. Epub 2011 Sep 21. PMID:21964294[1]

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

See Also

References

  1. ↑ Hirano H, Matsuura Y. Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL. Biochem Biophys Res Commun. 2011 Oct 22;414(2):373-8. doi:, 10.1016/j.bbrc.2011.09.079. Epub 2011 Sep 21. PMID:21964294 doi:10.1016/j.bbrc.2011.09.079

3tpm, resolution 2.10Å

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