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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 microt...

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Detalles Bibliográficos
Autor principal: Slep, Kevin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501478/
https://www.ncbi.nlm.nih.gov/pubmed/23185543
http://dx.doi.org/10.1371/journal.pone.0050097
Descripción
Sumario: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.