Identification of novel sphingolipid-binding motifs in mammalian membrane proteins

• Verfasst von: Björkholm, Patrik [VerfasserIn]
• Verfasst von: Ernst, Andreas M. [VerfasserIn]
• Verfasst von: Wieland, Felix T. [VerfasserIn]
• Verfasst von: Brügger, Britta [VerfasserIn]
• Titel: Identification of novel sphingolipid-binding motifs in mammalian membrane proteins
• Verf.angabe: Patrik Björkholm, Andreas M. Ernst, Moritz Hacke, Felix Wieland, Britta Brügger, Gunnar von Heijne
• E-Jahr: 2014
• Jahr: 2 May 2014
• Umfang: 5 S.
• Fussnoten: Gesehen am 28.07.2020
• Titel Quelle: Enthalten in: Biochimica et biophysica acta / Biomembranes
• Ort Quelle: Amsterdam : Elsevier, 1967
• Jahr Quelle: 2014
• Band/Heft Quelle: 1838(2014), 8, Seite 2066-2070
• ISSN Quelle: 1879-2642
• DOI: doi:10.1016/j.bbamem.2014.04.026
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Membrane protein
• Sach-SW: Sphingolipid
• Sach-SW: Transmembrane helix
• K10plus-PPN: 1725681536

Abstract

Specific interactions between transmembrane proteins and sphingolipids is a poorly understood phenomenon, and only a couple of instances have been identified. The best characterized example is the sphingolipid-binding motif VXXTLXXIY found in the transmembrane helix of the vesicular transport protein p24. Here, we have used a simple motif-probability algorithm (MOPRO) to identify proteins that contain putative sphingolipid-binding motifs in a dataset comprising proteomes from mammalian organisms. From these motif-containing candidate proteins, four with different numbers of transmembrane helices were selected for experimental study: i) major histocompatibility complex II Q alpha chain subtype (DQA1), ii) GPI-attachment protein 1 (GAA1), iii) tetraspanin-7 TSN7, and iv), metabotropic glutamate receptor 2 (GRM2). These candidates were subjected to photo-affinity labeling using radiolabeled sphingolipids, confirming all four candidate proteins as sphingolipid-binding proteins. The sphingolipid-binding motifs are enriched in the 7TM family of G-protein coupled receptors, predominantly in transmembrane helix 6. The ability of the motif-containing candidate proteins to bind sphingolipids with high specificity opens new perspectives on their respective regulation and function.