Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis

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 ar...

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Veröffentlicht in:The Journal of biological chemistry 2011-06, Vol.286 (23), p.20125-20129
Hauptverfasser: Truschel, Steven T., Sengupta, Debrup, Foote, Adam, Heroux, Annie, Macbeth, Mark R., Linstedt, Adam D.
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container_end_page 20129
container_issue 23
container_start_page 20125
container_title The Journal of biological chemistry
container_volume 286
creator Truschel, Steven T.
Sengupta, Debrup
Foote, Adam
Heroux, Annie
Macbeth, Mark R.
Linstedt, Adam D.
description 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.
doi_str_mv 10.1074/jbc.C111.245324
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subjects 60 APPLIED LIFE SCIENCES
BASIC BIOLOGICAL SCIENCES
CRYSTAL STRUCTURE
Crystallography, X-Ray
FUNCTIONALS
Golgi
Golgi Apparatus - chemistry
Golgi Apparatus - genetics
Golgi Apparatus - metabolism
Golgi Matrix Proteins
HeLa Cells
Humans
Intracellular Membranes - chemistry
Intracellular Membranes - metabolism
Membrane Biogenesis
Membrane Fusion
MEMBRANE PROTEINS
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Membrane Trafficking
MEMBRANES
PDZ Domains
Protein Folding
PROTEIN STRUCTURE
SPECIFICITY
title Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis
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