3wp0

Crystal structure of Dlg GK in complex with a phosphor-Lgl2 peptideCrystal structure of Dlg GK in complex with a phosphor-Lgl2 peptide

Structural highlights

3wp0 is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	3wp1
Gene:	Dlg4, Dlgh4, Psd95 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DLG4_RAT] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B.^[1] ^[2] [L2GL2_HUMAN] Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity.^[3]

Publication Abstract from PubMed

The tumor suppressors Discs Large (Dlg), Lethal giant larvae (Lgl) and Scribble are essential for the establishment and maintenance of epithelial cell polarity in metazoan. Dlg, Lgl and Scribble are known to interact strongly with each other genetically and form the evolutionarily conserved Scribble complex. Despite more than a decade of extensive research, it has not been demonstrated whether Dlg, Lgl and Scribble physically interact with each other. Here, we show that Dlg directly interacts with Lgl in a phosphorylation-dependent manner. Phosphorylation of any one of the three conserved Ser residues situated in the central linker region of Lgl is sufficient for its binding to the Dlg guanylate kinase (GK) domain. The crystal structures of the Dlg4 GK domain in complex with two phosphor-Lgl2 peptides reveal the molecular mechanism underlying the specific and phosphorylation-dependent Dlg/Lgl complex formation. In addition to providing a mechanistic basis underlying the regulated formation of the Scribble complex, the structure of the Dlg/Lgl complex may also serve as a starting point for designing specific Dlg inhibitors for targeting the Scribble complex formation.Cell Research advance online publication 11 February 2014; doi:10.1038/cr.2014.16.

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl.,Zhu J, Shang Y, Wan Q, Xia Y, Chen J, Du Q, Zhang M Cell Res. 2014 Feb 11. doi: 10.1038/cr.2014.16. PMID:24513855^[4]

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

References

↑ Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200
↑ Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101
↑ 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
↑ Zhu J, Shang Y, Wan Q, Xia Y, Chen J, Du Q, Zhang M. Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl. Cell Res. 2014 Feb 11. doi: 10.1038/cr.2014.16. PMID:24513855 doi:http://dx.doi.org/10.1038/cr.2014.16

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Hruska-Hageman AM, Benson CJ, Leonard AS, Price MP, Welsh MJ. PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current. J Biol Chem. 2004 Nov 5;279(45):46962-8. Epub 2004 Aug 17. PMID:15317815 doi:10.1074/jbc.M405874200

[2] Prange O, Wong TP, Gerrow K, Wang YT, El-Husseini A. A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13915-20. Epub 2004 Sep 9. PMID:15358863 doi:10.1073/pnas.0405939101

[3] 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

[4] Zhu J, Shang Y, Wan Q, Xia Y, Chen J, Du Q, Zhang M. Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl. Cell Res. 2014 Feb 11. doi: 10.1038/cr.2014.16. PMID:24513855 doi:http://dx.doi.org/10.1038/cr.2014.16

[1]

[2]

[3]

[4]