Sphingosine kinase

The Sphingosine Kinase Type 1 (SphK1) structure reveals a two domain alpha-beta architecture. ^[1] The catalytic site (used in converting sphingosine to S1P-see below in "function" section for more details) is in a hydrophobic cleft, located between the two domains. ^[1] This hydrophobic cleft is an ideal binding pocket for a hydrophobic lipid, like sphingosine (an 18-carbon amino alcohol with an unsaturated hydrocarbon chain). ^[1]

Function

Sphingolipids are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. ^[2] Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and pathogen defense. ^[2] Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system.

Sphingosine-1-Phosphate (S1P), a lipid within the sphingolipid class, is an important signaling molecule that can participate in intracellular and extracellular signaling. ^{[2] [3]} If meant to be an intracellular signaling molecule, S1P is important for cell survival, growth, and overall cell function.^[3] Alternatively, if S1P is meant to be an extracellular signaling molecule, later binding to one of five different S1P G-Protein Coupled Receptors on the same or different cell type, it is used to activate many signaling cascades important for cell response. ^[3] One important function of S1P, whether its fate serves intracellularly or extracellularly, is eliciting the immune response (i.e. lymphocyte trafficking), especially as a mechanism in pathogen defense. ^[3]

Sphingosine Kinase, existing in two isoenzyme forms, SphK1 and SphK2, creates S1P via the phosphorylation of sphingosine, the base moiety of all sphingolipids. ^[3] SphK1 is a central enzyme controlling the levels of S1P within the eukaryotic cell, and thus, is an important regulator of diverse cellular functions. ^[1]

Relevance

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

1. ↑ ^{1.0 1.1 1.2 1.3} Wang Z, Min X, Xiao SH, Johnstone S, Romanow W, Meininger D, Xu H, Liu J, Dai J, An S, Thibault S, Walker N. Molecular Basis of Sphingosine Kinase 1 Substrate Recognition and Catalysis. Structure. 2013 Apr 16. pii: S0969-2126(13)00086-5. doi:, 10.1016/j.str.2013.02.025. PMID:23602659 doi:http://dx.doi.org/10.1016/j.str.2013.02.025
2. ↑ ^{2.0 2.1 2.2} Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep. 2004 Aug;5(8):777-82. doi: 10.1038/sj.embor.7400208. PMID:15289826 doi:http://dx.doi.org/10.1038/sj.embor.7400208
3. ↑ ^{3.0 3.1 3.2 3.3 3.4} Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol. 2003 May;4(5):397-407. doi: 10.1038/nrm1103. PMID:12728273 doi:http://dx.doi.org/10.1038/nrm1103

• Privacy policy
• About Proteopedia
• Disclaimers