| Structural highlights
Function
[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.[1] [2] [3] [4] [5] [6]
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[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ 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
- ↑ 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. FASEB J. 2010 Aug 11. PMID:20702775 doi:10.1096/fj.10-163857
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