4g69 | pdb_00004g69
Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex
Structural highlights
FunctionDLG1_HUMAN Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe 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. Structure of the Human Discs Large 1 PDZ2- Adenomatous Polyposis Coli Cytoskeletal Polarity Complex: Insight into Peptide Engagement and PDZ Clustering.,Slep KC PLoS One. 2012;7(11):e50097. doi: 10.1371/journal.pone.0050097. Epub 2012 Nov 19. PMID:23185543[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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