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5gxw

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Revision as of 09:57, 22 November 2017

Importin and NuMA complex

Structural highlights

5gxw is a 2 chain structure with sequence from Human 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), NUMA1, NMP22, NUMA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[NUMA1_HUMAN] Acute promyelocytic leukemia.

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. [NUMA1_HUMAN] Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority if the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functionning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions.^[1]

Publication Abstract from PubMed

Ran-guanosine triphosphatase orchestrates mitotic spindle assembly by modulation of the interaction between Importin-alpha/-beta and spindle assembly factors (SAFs). The inhibition of SAFs performed by importins needs to be done without much sequestration from abundant nuclear localization signal (NLS) -containing proteins. However, the molecular mechanisms that determine NLS-binding selectivity and that inhibit activity of Importin-beta-regulated SAFs (e.g., nuclear mitotic apparatus protein [NuMA]) remain undefined. Here, we present a crystal structure of the Importin-alpha-NuMA C terminus complex showing a novel binding pattern that accounts for selective NLS recognition. We demonstrate that, in the presence of Importin-alpha, Importin-beta inhibits the microtubule-binding function of NuMA. Further, we have identified a high-affinity microtubule-binding region that lies carboxyl-terminal to the NLS, which is sterically masked by Importin-beta on being bound by Importin-alpha. Our study provides mechanistic evidence of how Importin-alpha/-beta regulates the NuMA functioning required for assembly of higher-order microtubule structures, further illuminating how Ran-governed transport factors regulate diverse SAFs and accommodate various cell demands.

Regulation of mitotic spindle assembly factor NuMA by Importin-beta.,Chang CC, Huang TL, Shimamoto Y, Tsai SY, Hsia KC J Cell Biol. 2017 Sep 22. pii: jcb.201705168. doi: 10.1083/jcb.201705168. PMID:28939615^[2]

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

References

↑ Silk AD, Holland AJ, Cleveland DW. Requirements for NuMA in maintenance and establishment of mammalian spindle poles. J Cell Biol. 2009 Mar 9;184(5):677-90. doi: 10.1083/jcb.200810091. Epub 2009 Mar , 2. PMID:19255246 doi:http://dx.doi.org/10.1083/jcb.200810091
↑ Chang CC, Huang TL, Shimamoto Y, Tsai SY, Hsia KC. Regulation of mitotic spindle assembly factor NuMA by Importin-beta. J Cell Biol. 2017 Sep 22. pii: jcb.201705168. doi: 10.1083/jcb.201705168. PMID:28939615 doi:http://dx.doi.org/10.1083/jcb.201705168

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gxw"

@@ Line 3: / Line 3: @@
 <StructureSection load='5gxw' size='340' side='right' caption='[[5gxw]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5gxw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GXW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GXW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5gxw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] 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=5GXW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GXW 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=5gxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gxw OCA], [http://pdbe.org/5gxw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gxw RCSB], [http://www.ebi.ac.uk/pdbsum/5gxw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gxw ProSAT]</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]), NUMA1, NMP22, NUMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5gxw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gxw OCA], [http://pdbe.org/5gxw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gxw RCSB], [http://www.ebi.ac.uk/pdbsum/5gxw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gxw ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Chang, C C]]
 [[Category: Hsia, K C]]

5gxw

From Proteopedia

Revision as of 09:57, 22 November 2017

Importin and NuMA complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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