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| | <StructureSection load='3lra' size='340' side='right'caption='[[3lra]], [[Resolution|resolution]] 2.95Å' scene=''> | | <StructureSection load='3lra' size='340' side='right'caption='[[3lra]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lra]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LRA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lra]] is a 1 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=3LRA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LRA 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=3lra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lra OCA], [https://pdbe.org/3lra PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lra RCSB], [https://www.ebi.ac.uk/pdbsum/3lra PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lra 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]] 2.95Å</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=3lra FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lra OCA], [https://pdbe.org/3lra PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lra RCSB], [https://www.ebi.ac.uk/pdbsum/3lra PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lra ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> | + | [https://www.uniprot.org/uniprot/LIN7C_HUMAN LIN7C_HUMAN] Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.[UniProtKB:O88952][https://www.uniprot.org/uniprot/MPP7_HUMAN MPP7_HUMAN] Acts as an important adapter that promotes epithelial cell polarity and tight junction formation via its interaction with DLG1. Involved in the assembly of protein complexes at sites of cell-cell contact.<ref>PMID:17332497</ref> [https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The establishment of epithelial cell polarity requires the assembly of multiprotein complexes and is crucial during epithelial morphogenesis. Three scaffolding proteins, Dlg1, MPP7, and Mals3, can be assembled to form a complex that functions in the establishment and maintenance of apicobasal polarity in epithelial tissues through their L27 domains. Here we report the crystal structure of a 4-L27-domain complex derived from the human tripartite complex Dlg1-MPP7-Mals3 in combination with paramagnetic relaxation enhancement measurements. The heterotrimer consists of 2 pairs of heterodimeric L27 domains. These 2 dimers are asymmetric due to the large difference between the N- and C-terminal tandem L27 domain of MPP7. Structural analysis combined with biochemical experiments further reveals that the loop alphaA-alphaB and helix alphaB of the C-terminal L27 domain of MPP7 play a critical role in assembling the entire tripartite complex, suggesting a synergistic tandem L27-mediated assembling event.-Yang, X., Xie, X., Chen, L., Zhou, H., Wang, Z., Zhao, W., Tian, R., Zhang, R., Tian, C., Long, J., Shen, Y. Structural basis for tandem L27 domain-mediated polymerization.
| + | |
| - | | + | |
| - | Structural basis for tandem L27 domain-mediated polymerization.,Yang X, Xie X, Chen L, Zhou H, Wang Z, Zhao W, Tian R, Zhang R, Tian C, Long J, Shen Y FASEB J. 2010 Aug 11. PMID:20702775<ref>PMID:20702775</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3lra" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Long, J]] | + | [[Category: Long J]] |
| - | [[Category: Shen, Y]] | + | [[Category: Shen Y]] |
| - | [[Category: Xie, X]] | + | [[Category: Xie X]] |
| - | [[Category: Yang, X]] | + | [[Category: Yang X]] |
| - | [[Category: Cell junction]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Exocytosis]]
| + | |
| - | [[Category: Host-virus interaction]]
| + | |
| - | [[Category: L27 tetramer]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Postsynaptic cell membrane]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Synaptosome]]
| + | |
| - | [[Category: Tight junction]]
| + | |
| - | [[Category: Transport]]
| + | |
| - | [[Category: Tripartite complex]]
| + | |
| Structural highlights
Function
LIN7C_HUMAN Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.[UniProtKB:O88952]MPP7_HUMAN Acts as an important adapter that promotes epithelial cell polarity and tight junction formation via its interaction with DLG1. Involved in the assembly of protein complexes at sites of cell-cell contact.[1] DLG1_HUMAN Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.[2] [3] [4] [5] [6] [7]
References
- ↑ Stucke VM, Timmerman E, Vandekerckhove J, Gevaert K, Hall A. The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation. Mol Biol Cell. 2007 May;18(5):1744-55. Epub 2007 Mar 1. PMID:17332497 doi:10.1091/mbc.E06-11-0980
- ↑ Ishidate T, Matsumine A, Toyoshima K, Akiyama T. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene. 2000 Jan 20;19(3):365-72. PMID:10656683 doi:10.1038/sj.onc.1203309
- ↑ Godreau D, Vranckx R, Maguy A, Rucker-Martin C, Goyenvalle C, Abdelshafy S, Tessier S, Couetil JP, Hatem SN. Expression, regulation and role of the MAGUK protein SAP-97 in human atrial myocardium. Cardiovasc Res. 2002 Dec;56(3):433-42. PMID:12445884
- ↑ Laprise P, Viel A, Rivard N. Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. J Biol Chem. 2004 Mar 12;279(11):10157-66. Epub 2003 Dec 29. PMID:14699157 doi:10.1074/jbc.M309843200
- ↑ Xavier R, Rabizadeh S, Ishiguro K, Andre N, Ortiz JB, Wachtel H, Morris DG, Lopez-Ilasaca M, Shaw AC, Swat W, Seed B. Discs large (Dlg1) complexes in lymphocyte activation. J Cell Biol. 2004 Jul 19;166(2):173-8. PMID:15263016 doi:10.1083/jcb.200309044
- ↑ El-Haou S, Balse E, Neyroud N, Dilanian G, Gavillet B, Abriel H, Coulombe A, Jeromin A, Hatem SN. Kv4 potassium channels form a tripartite complex with the anchoring protein SAP97 and CaMKII in cardiac myocytes. Circ Res. 2009 Mar 27;104(6):758-69. doi: 10.1161/CIRCRESAHA.108.191007. Epub, 2009 Feb 12. PMID:19213956 doi:10.1161/CIRCRESAHA.108.191007
- ↑ Sabio G, Cerezo-Guisado MI, Del Reino P, Inesta-Vaquera FA, Rousseau S, Arthur JS, Campbell DG, Centeno F, Cuenda A. p38gamma regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock. J Cell Sci. 2010 Aug 1;123(Pt 15):2596-604. doi: 10.1242/jcs.066514. Epub 2010, Jul 6. PMID:20605917 doi:10.1242/jcs.066514
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