Identification of novel sphingolipid-binding motifs in mammalian membrane proteins
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 protei...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2 May 2014
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| In: |
Biochimica et biophysica acta. Biomembranes
Year: 2014, Jahrgang: 1838, Heft: 8, Pages: 2066-2070 |
| ISSN: | 1879-2642 |
| DOI: | 10.1016/j.bbamem.2014.04.026 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbamem.2014.04.026 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0005273614001618 
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| Verfasserangaben: | Patrik Björkholm, Andreas M. Ernst, Moritz Hacke, Felix Wieland, Britta Brügger, Gunnar von Heijne |
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| 520 | |a 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. | ||
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