title: The structure of the PDZ3-SH3-GuK tandem of ZO-1 protein suggests a supramodular organization of the membrane-associated guanylate kinase (MAGUK) family scaffold protein core.
abstract: Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tethering membrane receptors, adhesion molecules, and macromolecular signaling complexes for tissue developments, cell-cell communications, and intracellular signal transductions. The defining feature of the MAGUK family scaffolds is that each member contains a conserved core consisting of a PSD-95/Dlg/ZO-1 (PDZ) domain, an Src homology 3 (SH3) domain, and a catalytically inactive guanylate kinase (GuK) domain arranged in tandem, although the structural features and functional implications of the PDZ-SH3-GuK tandem arrangement are unclear. The structure of the ZO-1 PDZ3-SH3-GuK tandem solved in this study reveals that the PDZ domain directly interacts with the SH3-GuK module, forming a structural supramodule with distinct target binding properties with respect to the isolated domains. Structure-based sequence analysis suggests that the PDZ-SH3-GuK tandems of other members of the MAGUK family also form supramodules.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Pan
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.forename: Haoyue
authors.initials: H
authors.lastname: Yu
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D018360:Crystallography, X-Ray; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D062826:Zonula Occludens-1 Protein; D018909:src Homology Domains
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D006162:Guanylate Cyclase