3UAT

Guanylate Kinase Domains of the MAGUK Family Scaffold Proteins as Specific Phospho-Protein Binding Modules

Summary for 3UAT

• Entry DOI: 10.2210/pdb3uat/pdb
• Descriptor: Disks large homolog 1, phosphor-LGN peptide (3 entities in total)
• Functional Keywords: dlg gk domain, phosphor-peptide binding module, phosphor-lgn, peptide binding protein
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Membrane; Peripheral membrane protein (By similarity): Q62696
• Total number of polymer chains: 2
• Total formula weight: 36551.24

Authors

Shang, Y.,Zhu, J.,Wen, W.,Zhang, M. (deposition date: 2011-10-22, release date: 2011-12-07, Last modification date: 2024-11-20)

Primary citation

Zhu, J.,Shang, Y.,Xia, C.,Wang, W.,Wen, W.,Zhang, M.
Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules
Embo J., 2011

PubMed Abstract: Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/pThr-binding pocket. Residues both N- and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/target interactions indicates that MAGUK scaffold-mediated signalling complex organizations are dynamically regulated.

PubMed: 22117215
DOI: 10.1038/emboj.2011.428

Experimental method

X-RAY DIFFRACTION (2.7 Å)