3WP1

Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

Summary for 3WP1

• Entry DOI: 10.2210/pdb3wp1/pdb
• Related: 3WP0
• Descriptor: Disks large homolog 4, Lethal(2) giant larvae protein homolog 2, SULFATE ION, ... (4 entities in total)
• Functional Keywords: maguk, phosphorylation, cell polarity, tumor suppressors, phosphorylation dependent, peptide binding protein
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cell membrane; Peripheral membrane protein: P31016; Cytoplasm: Q6P1M3
• Total number of polymer chains: 2
• Total formula weight: 24091.08

Authors

Zhu, J.,Shang, Y.,Wan, Q.,Xia, Y.,Chen, J.,Du, Q.,Zhang, M. (deposition date: 2014-01-08, release date: 2014-03-19, Last modification date: 2024-10-16)

Primary citation

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., 24:451-463, 2014

PubMed Abstract: 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.

PubMed: 24513855
DOI: 10.1038/cr.2014.16

Experimental method

X-RAY DIFFRACTION (2.804 Å)