title: Structure of the membrane-tethering GRASP domain reveals a unique PDZ ligand interaction that mediates Golgi biogenesis.
abstract: Biogenesis of the ribbon-like membrane network of the mammalian Golgi requires membrane tethering by the conserved GRASP domain in GRASP65 and GRASP55, yet the tethering mechanism is not fully understood. Here, we report the crystal structure of the GRASP55 GRASP domain, which revealed an unusual arrangement of two tandem PDZ folds that more closely resemble prokaryotic PDZ domains. Biochemical and functional data indicated that the interaction between the ligand-binding pocket of PDZ1 and an internal ligand on PDZ2 mediates the GRASP self-interaction, and structural analyses suggest that this occurs via a unique mode of internal PDZ ligand recognition. Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Truschel
authors.forename: Debrup
authors.initials: D
authors.lastname: Sengupta
authors.forename: Adam
authors.initials: A
authors.lastname: Foote
authors.forename: Annie
authors.initials: A
authors.lastname: Heroux
authors.forename: Mark R
authors.initials: MR
authors.lastname: Macbeth
authors.forename: Adam D
authors.initials: AD
authors.lastname: Linstedt
mesh_terms: D018360:Crystallography, X-Ray; D006056:Golgi Apparatus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains; D017510:Protein Folding
chemical_list: C108705:GORASP1 protein, human; C122048:GORASP2 protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins