7YKI

Crystal structure of MAGI2 PDZ0-GK domain in complex with phospho-SAPAP1 GBR3 peptide

Summary for 7YKI

• Entry DOI: 10.2210/pdb7yki/pdb
• Descriptor: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2, SAPAP1, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: magi2, pdz0-gk, sapap1, gbr3, phosphorylated peptide, peptide binding protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 4
• Total formula weight: 56080.67

Authors

Zhang, M.,Lin, L.,Zhu, J. (deposition date: 2022-07-22, release date: 2023-08-02, Last modification date: 2024-10-09)

Primary citation

Zhang, M.,Cao, A.,Lin, L.,Chen, Y.,Shang, Y.,Wang, C.,Zhang, M.,Zhu, J.
Phosphorylation-dependent recognition of diverse protein targets by the cryptic GK domain of MAGI MAGUKs.
Sci Adv, 9:eadf3295-eadf3295, 2023

PubMed Abstract: Dynamic signal transduction requires the rapid assembly and disassembly of signaling complexes, often mediated by phosphoprotein binding modules. The guanylate kinase-like (GK) domain of the membrane-associated guanylate kinases (MAGUKs) is such a module orchestrating signaling at cellular junctions. The MAGI subfamily of MAGUKs contains a truncated GK domain with unknown structure and function, although they participate in diverse physiological and pathological processes. Here, we demonstrate that the truncated GK domain of MAGI2 interacts with its adjacent PDZ0 domain to form a structural supramodule capable of recognizing phosphoproteins. A conserved phosphorylation-dependent binding motif for PDZ0-GK is delineated, which leads to identification of a set of previously unknown binding partners. We explore the structure and function of the MAGI2-target complex with an inhibitory peptide derived from the consensus motif. Our work reveals an action mechanism of the cryptic MAGI GKs and broadens our understanding of the target recognition rules of phosphoprotein binding modules.

PubMed: 37163606
DOI: 10.1126/sciadv.adf3295

Experimental method

X-RAY DIFFRACTION (2 Å)