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 |
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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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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.C111.245324</identifier><identifier>PMID: 21515684</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>The Journal of biological chemistry, 2011-06, Vol.286 (23), p.20125-20129</ispartof><rights>2011 © 2011 ASBMB. 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Our data uncover the structural basis for ligand specificity and provide insight into the mechanism of GRASP-dependent membrane tethering of analogous Golgi cisternae.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>CRYSTAL STRUCTURE</subject><subject>Crystallography, X-Ray</subject><subject>FUNCTIONALS</subject><subject>Golgi</subject><subject>Golgi Apparatus - chemistry</subject><subject>Golgi Apparatus - genetics</subject><subject>Golgi Apparatus - metabolism</subject><subject>Golgi Matrix Proteins</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Intracellular Membranes - chemistry</subject><subject>Intracellular Membranes - metabolism</subject><subject>Membrane Biogenesis</subject><subject>Membrane Fusion</subject><subject>MEMBRANE PROTEINS</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Trafficking</subject><subject>MEMBRANES</subject><subject>PDZ Domains</subject><subject>Protein Folding</subject><subject>PROTEIN STRUCTURE</subject><subject>SPECIFICITY</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1vFCEYxonR2HX17M0QL55mCwzMx8WkbnVtssamH4nxQhh4Z5ZmFiowa_zvZTO10YNcCOHh4XmfH0KvKVlRUvPTu06v1pTSFeOiZPwJWlDSlEUp6LenaEEIo0XLRHOCXsR4R_LiLX2OThgVVFQNX6Cf1ylMOk0BsO9x2gH-AvsuKAdFgnwM1g14c3V2fYnP_V5Zh6_gAGqMWOFbZ39MgC_Pv-OtHZQz-MIlCEon6x2-2amUzYxVCSLe-HGw-IP1AziINr5Ez_rsAq8e9iW6_fTxZv252H7dXKzPtoXmVZuKztSCmcowwirVl00nKtZ0Hcsj15Qwo5Vq-5ZRU7aKdpoDA0brpswHXhujyyV6P_veT90ejAaXghrlfbB7FX5Jr6z898bZnRz8QZaUUZ6dlujtbOBjsjJqm0DvtHcOdJI5ghCEZNG7h1-Cz5XEJPc2ahjH3KOfomxqInidcWTl6azUwccYoH-MQok8IpUZqTwilTPS_OLN3xM86v8wzIJ2FkDu8WAhHFOC07n6cAxpvP2v-W-IhrDV</recordid><startdate>20110610</startdate><enddate>20110610</enddate><creator>Truschel, Steven T.</creator><creator>Sengupta, Debrup</creator><creator>Foote, Adam</creator><creator>Heroux, Annie</creator><creator>Macbeth, Mark R.</creator><creator>Linstedt, Adam D.</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20110610</creationdate><title>Structure of the Membrane-tethering GRASP Domain Reveals a Unique PDZ Ligand Interaction That Mediates Golgi Biogenesis</title><author>Truschel, Steven T. ; 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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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21515684</pmid><doi>10.1074/jbc.C111.245324</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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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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