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From Proteopedia
Crystal Structure of the GRASP65-GM130 C-terminal peptide complex
Structural highlights
Function[GORS1_HUMAN] Stacking factor involved in the postmitotic assembly of Golgi stacks from mitotic Golgi fragments. Key structural protein required for the maintenance of the Golgi apparatus integrity: its caspase-mediated cleavage is required for fragmentation of the Golgi during apoptosis (By similarity). Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes (PubMed:16489344).[UniProtKB:O35254][1] [GOGA2_HUMAN] Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane. Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401).[UniProtKB:Q62839][UniProtKB:Q921M4][2] [3] [4] [5] [6] [7] Publication Abstract from PubMedGM130 and GRASP65 are Golgi peripheral membrane proteins that play a key role in Golgi stacking and vesicle tethering. However, the molecular details of their interaction and their structural role as a functional unit remain unclear. Here, we present the crystal structure of the PDZ domains of GRASP65 in complex with the GM130 C-terminal peptide at 1.96-A resolution. In contrast to previous findings proposing that GM130 interacts with GRASP65 at the PDZ2 domain only, our crystal structure of the complex indicates that GM130 binds to GRASP65 at two distinct sites concurrently and that both the PDZ1 and PDZ2 domains of GRASP65 participate in this molecular interaction. Mutagenesis experiments support these structural observations and demonstrate that they are required for GRASP65-GM130 association. Structural Basis for the Interaction between the Golgi Reassembly-stacking Protein GRASP65 and the Golgi Matrix Protein GM130.,Hu F, Shi X, Li B, Huang X, Morelli X, Shi N J Biol Chem. 2015 Oct 30;290(44):26373-82. doi: 10.1074/jbc.M115.657940. Epub, 2015 Sep 11. PMID:26363069[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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