| Structural highlights
Function
[C43BP_HUMAN] Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.[1] [2] [3] [4]
Publication Abstract from PubMed
Ceramide transport from the endoplasmic reticulum to the Golgi apparatus is crucial in sphingolipid biosynthesis, and the process relies on the ceramide trafficking protein (CERT), which contains pleckstrin homology (PH) and StAR-related lipid transfer domains. The CERT PH domain specifically recognizes phosphatidylinositol 4-monophosphate (PtdIns(4)P), a characteristic phosphoinositide in the Golgi membrane, and is indispensable for the endoplasmic reticulum-to-Golgi transport of ceramide by CERT. In this study, we determined the three-dimensional structure of the CERT PH domain by using solution NMR techniques. The structure revealed the presence of a characteristic basic groove near the canonical PtdIns(4)P recognition site. An extensive interaction study using NMR and other biophysical techniques revealed that the basic groove coordinates the CERT PH domain for efficient PtdIns(4)P recognition and localization in the Golgi apparatus. The notion was also supported by Golgi mislocalization of the CERT mutants in living cells. The distinctive binding modes reflect the functions of PH domains, as the basic groove is conserved only in the PH domains involved with the PtdIns(4)P-dependent lipid transport activity but not in those with the signal transduction activity.
Structural basis for the Golgi association by the pleckstrin homology domain of the ceramide trafficking protein (CERT).,Sugiki T, Takeuchi K, Yamaji T, Takano T, Tokunaga Y, Kumagai K, Hanada K, Takahashi H, Shimada I J Biol Chem. 2012 Sep 28;287(40):33706-18. Epub 2012 Aug 6. PMID:22869376[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M. Molecular machinery for non-vesicular trafficking of ceramide. Nature. 2003 Dec 18;426(6968):803-9. PMID:14685229 doi:http://dx.doi.org/10.1038/nature02188
- ↑ Fugmann T, Hausser A, Schoffler P, Schmid S, Pfizenmaier K, Olayioye MA. Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J Cell Biol. 2007 Jul 2;178(1):15-22. Epub 2007 Jun 25. PMID:17591919 doi:http://dx.doi.org/jcb.200612017
- ↑ Kudo N, Kumagai K, Tomishige N, Yamaji T, Wakatsuki S, Nishijima M, Hanada K, Kato R. Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):488-93. Epub 2008 Jan 9. PMID:18184806
- ↑ Kudo N, Kumagai K, Matsubara R, Kobayashi S, Hanada K, Wakatsuki S, Kato R. Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer. J Mol Biol. 2010 Feb 19;396(2):245-51. Epub 2009 Dec 28. PMID:20036255 doi:10.1016/j.jmb.2009.12.029
- ↑ Sugiki T, Takeuchi K, Yamaji T, Takano T, Tokunaga Y, Kumagai K, Hanada K, Takahashi H, Shimada I. Structural basis for the Golgi association by the pleckstrin homology domain of the ceramide trafficking protein (CERT). J Biol Chem. 2012 Sep 28;287(40):33706-18. Epub 2012 Aug 6. PMID:22869376 doi:http://dx.doi.org/10.1074/jbc.M112.367730
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