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5a6c

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Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation

Structural highlights

5a6c is a 2 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 2.901Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AFAD_HUMAN Note=A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein.GPSM2_HUMAN Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Chudley-McCullough syndrome. Chudley-McCullough syndrome (CMCS) [MIM:604213: An autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal. Note=The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2]

Function

AFAD_HUMAN Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton.GPSM2_HUMAN Plays an important role in spindle pole orientation. Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions.^[3]

Publication Abstract from PubMed

Polarized epithelia form by oriented cell divisions in which the mitotic spindle aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral microtubules via the protein LGN. We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts. Molecularly, Afadin binds directly and concomitantly to F-actin and to LGN. We determined the crystallographic structure of human Afadin in complex with LGN and show that it resembles the LGN-NuMA complex. In mitosis, Afadin is necessary for cortical accumulation of LGN and NuMA above the spindle poles, in an F-actin-dependent manner. Collectively, our results depict Afadin as a molecular hub governing the enrichment of LGN and NuMA at the cortex. To our knowledge, Afadin is the first-described mechanical anchor between dynein and cortical F-actin.

Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.,Carminati M, Gallini S, Pirovano L, Alfieri A, Bisi S, Mapelli M Nat Struct Mol Biol. 2016 Jan 11. doi: 10.1038/nsmb.3152. PMID:26751642^[4]

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

References

↑ Walsh T, Shahin H, Elkan-Miller T, Lee MK, Thornton AM, Roeb W, Abu Rayyan A, Loulus S, Avraham KB, King MC, Kanaan M. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. Am J Hum Genet. 2010 Jul 9;87(1):90-4. doi: 10.1016/j.ajhg.2010.05.010. Epub 2010, Jun 17. PMID:20602914 doi:10.1016/j.ajhg.2010.05.010
↑ Doherty D, Chudley AE, Coghlan G, Ishak GE, Innes AM, Lemire EG, Rogers RC, Mhanni AA, Phelps IG, Jones SJ, Zhan SH, Fejes AP, Shahin H, Kanaan M, Akay H, Tekin M, Triggs-Raine B, Zelinski T. GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome. Am J Hum Genet. 2012 Jun 8;90(6):1088-93. doi: 10.1016/j.ajhg.2012.04.008. Epub, 2012 May 10. PMID:22578326 doi:10.1016/j.ajhg.2012.04.008
↑ Yasumi M, Sakisaka T, Hoshino T, Kimura T, Sakamoto Y, Yamanaka T, Ohno S, Takai Y. Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division. J Biol Chem. 2005 Feb 25;280(8):6761-5. Epub 2005 Jan 4. PMID:15632202 doi:C400440200
↑ Carminati M, Gallini S, Pirovano L, Alfieri A, Bisi S, Mapelli M. Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation. Nat Struct Mol Biol. 2016 Jan 11. doi: 10.1038/nsmb.3152. PMID:26751642 doi:http://dx.doi.org/10.1038/nsmb.3152

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/5a6c"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5a6c]] is a 2 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=5A6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A6C FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.901&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5a6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a6c OCA], [https://pdbe.org/5a6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a6c RCSB], [https://www.ebi.ac.uk/pdbsum/5a6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a6c ProSAT]</span></td></tr>
 </table>

5a6c

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Current revision

Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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