The Discs large (Dlg) protein, first identified in Drosophila, is the foundational member of a significant group of proteins known as membrane-associated guanylate kinase homologs (MAGUKs).
Understanding MAGUKs
MAGUKs are a diverse family of scaffolding proteins primarily found at the cell membrane. They play crucial roles in organizing protein complexes at specialized membrane domains, such as synapses in nerve cells or cell-cell junctions in epithelia. Their function often involves linking receptors, ion channels, and signaling molecules to the underlying cytoskeleton.
Key Features of DLG and MAGUKs
As the prototypic MAGUK member, the DLG protein shares the characteristic structural organization of this family, which is defined by a specific series of peptide domains. According to the provided reference, these domains include:
- PDZ Domains: These are protein interaction modules that typically bind to specific peptide sequences (often C-terminal tails) on other proteins. MAGUKs, including DLG, can contain one or three DHR/PDZ domains. These domains are critical for recruiting various partner proteins.
- SH3 Domain: An SH3 (Src homology 3) domain is another protein interaction module, commonly involved in binding to proline-rich motifs. This domain facilitates the assembly of signaling complexes.
- GUK Domain: Despite the "guanylate kinase homolog" name, the GUK domain in most MAGUKs, including DLG, lacks enzymatic activity. Instead, it serves as a platform for protein-protein interactions, often binding to other proteins or even interacting with the SH3 domain.
This modular architecture allows DLG and other MAGUKs to act as central hubs for the assembly of complex macromolecular structures at the membrane, influencing cell polarity, signaling, and junction integrity.