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| | ==Structure of human SUN-KASH complex== | | ==Structure of human SUN-KASH complex== |
| - | <StructureSection load='4fi9' size='340' side='right' caption='[[4fi9]], [[Resolution|resolution]] 3.05Å' scene=''> | + | <StructureSection load='4fi9' size='340' side='right'caption='[[4fi9]], [[Resolution|resolution]] 3.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fi9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FI9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FI9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fi9]] 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=4FI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FI9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SUN2, FRIGG, KIAA0668, RAB5IP, UNC84B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 3.05Å</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=4fi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fi9 OCA], [http://pdbe.org/4fi9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fi9 RCSB], [http://www.ebi.ac.uk/pdbsum/4fi9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fi9 ProSAT]</span></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=4fi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fi9 OCA], [https://pdbe.org/4fi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fi9 RCSB], [https://www.ebi.ac.uk/pdbsum/4fi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fi9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/SYNE2_HUMAN SYNE2_HUMAN]] Autosomal dominant Emery-Dreifuss muscular dystrophy. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SUN2_HUMAN SUN2_HUMAN]] Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.<ref>PMID:18396275</ref> [[http://www.uniprot.org/uniprot/SYNE2_HUMAN SYNE2_HUMAN]] Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Involved in the maintenance of nuclear organization and structural integrity. Connects nuclei to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for centrosome migration to the apical cell surface during early ciliogenesis.<ref>PMID:12118075</ref> <ref>PMID:18396275</ref> <ref>PMID:19596800</ref> <ref>PMID:20724637</ref> | + | [https://www.uniprot.org/uniprot/SUN2_HUMAN SUN2_HUMAN] Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.<ref>PMID:18396275</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Shi, Z B]] | + | [[Category: Large Structures]] |
| - | [[Category: Wang, W J]] | + | [[Category: Shi ZB]] |
| - | [[Category: Linc complex]] | + | [[Category: Wang WJ]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Transmembrane protein]]
| + | |
| Structural highlights
Function
SUN2_HUMAN Component of SUN-protein-containing multivariate complexes also called LINC complexes which link the nucleoskeleton and cytoskeleton by providing versatile outer nuclear membrane attachment sites for cytoskeletal filaments. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5.[1]
Publication Abstract from PubMed
Linker of the nucleoskeleton and the cytoskeleton (LINC) complexes are composed of SUN and KASH domain-containing proteins and bridge the inner and outer membranes of the nuclear envelope. LINC complexes play critical roles in nuclear positioning, cell polarization and cellular stiffness. Previously, we reported the homotrimeric structure of human SUN2. We have now determined the crystal structure of the human SUN2-KASH complex. In the complex structure, the SUN domain homotrimer binds to three independent "hook"-like KASH peptides. The overall conformation of the SUN domain in the complex closely resembles the SUN domain in its apo state. A major conformational change involves the AA'-loop of KASH-bound SUN domain, which rearranges to form a mini beta-sheet that interacts with the KASH peptide. The PPPT motif of the KASH domain fits tightly into a hydrophobic pocket on the homotrimeric interface of the SUN domain, which we termed the BI-pocket. Moreover, two adjacent protomers of the SUN domain homotrimer sandwich the KASH domain by hydrophobic interaction and hydrogen bonding. Mutations of these binding sites disrupt or reduce the association between the SUN and KASH domains in vitro. In addition, transfection of wild-type, but not mutant, SUN2 promotes cell migration in Ovcar-3 cells. These results provide a structural model of the LINC complex, which is essential for additional study of the physical and functional coupling between the cytoplasm and the nucleoplasm.
Structural insights into SUN-KASH complexes across the nuclear envelope.,Wang W, Shi Z, Jiao S, Chen C, Wang H, Liu G, Wang Q, Zhao Y, Greene MI, Zhou Z Cell Res. 2012 Oct;22(10):1440-52. doi: 10.1038/cr.2012.126. Epub 2012 Sep 4. PMID:22945352[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stewart-Hutchinson PJ, Hale CM, Wirtz D, Hodzic D. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness. Exp Cell Res. 2008 May 1;314(8):1892-905. doi: 10.1016/j.yexcr.2008.02.022. Epub , 2008 Mar 12. PMID:18396275 doi:http://dx.doi.org/10.1016/j.yexcr.2008.02.022
- ↑ Wang W, Shi Z, Jiao S, Chen C, Wang H, Liu G, Wang Q, Zhao Y, Greene MI, Zhou Z. Structural insights into SUN-KASH complexes across the nuclear envelope. Cell Res. 2012 Oct;22(10):1440-52. doi: 10.1038/cr.2012.126. Epub 2012 Sep 4. PMID:22945352 doi:http://dx.doi.org/10.1038/cr.2012.126
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