Structure of the human discs large 1 pdz2- Adenomatous polyposis coli cytoskeletal polarity complex: insight into peptide engagement and pdz clustering.
The membrane associated guanylate kinase (MAGUK) family member, human Discs
Large 1 (hDlg1) uses a PDZ domain array to interact with the polarity
determinant, the Adenomatous Polyposis Coli (APC) microtubule plus end binding
protein. The hDLG1-APC complex mediates a dynamic attachment between microtubule
plus ends and polarized cortical determinants in epithelial cells, stem cells,
and neuronal synapses. Using its multi-domain architecture, hDlg1 both scaffolds
and regulates the polarity factors it engages. Molecular details underlying the
hDlg1-APC interaction and insight into how the hDlg1 PDZ array may cluster and
regulate its binding factors remain to be determined. Here, I present the
crystal structure of the hDlg1 PDZ2-APC complex and the molecular determinants
that mediate APC binding. The hDlg1 PDZ2-APC complex also provides insight into
potential modes of ligand-dependent PDZ domain clustering that may parallel Dlg
scaffold regulatory mechanisms. The hDlg1 PDZ2-APC complex presented here
represents a core biological complex that bridges polarized cortical
determinants with the dynamic microtubule cytoskeleton.
