Structure of human nSMase2 reveals an interdomain allosteric activation mechanism for ceramide generation

Proceedings of the National Academy of Sciences of the United States of America

Volumn 114, Issue 28, 2017, Pages E5549-E5558

  Airola, Michael V ^a,b   Shanbhogue, Prajna ^b   Shamseddine, Achraf A ^b   Guja, Kip E ^b   Senkal, Can E ^a,b   Maini, Rohan ^b   Bartke, Nana ^c,d   Wu, Bill X ^d   Obeid, Lina M ^a,b,e   Garcia Diaz, Miguel ^b   Hannun, Yusuf A ^a,b   Russell, David W ^f  

^a Stony Brook School of Dental Medicine   (United States)

^b STONY BROOK UNIVERSITY   (United States)

^c Danone Research Centre for Specialised Nutrition   (Singapore)

^d MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^e VETERANS AFFAIRS MEDICAL CENTER   (United States)

^f UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Ceramide; Crystallography; Enzyme; Lipid; Sphingomyelinase

Indexed keywords

3,3' (1,4 PHENYLENE)BIS[N [4 (4,5 DIHYDRO 1H IMIDAZOL 2 YL)PHENYL]ACRYLAMIDE]; ASPARTIC ACID; BACTERIAL ENZYME; CERAMIDE; DEOXYRIBONUCLEASE I; NEUTRAL SPHINGOMYELINASE 2; PHOSPHATIDYLSERINE; SPHINGOMYELIN PHOSPHODIESTERASE; UNCLASSIFIED DRUG; ANILINE DERIVATIVE; BENZYLIDENE DERIVATIVE; LIPID; PROTEIN BINDING; SMPD3 PROTEIN, HUMAN;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; CATALYSIS; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME INHIBITION; ENZYME STRUCTURE; GENETIC CONSERVATION; HUMAN; HYDROLYSIS; HYDROPHOBICITY; LIPOGENESIS; MEMBRANE; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN MOTIF; ALLOSTERIC SITE; BIOSYNTHESIS; CELL MEMBRANE; CHEMISTRY; MCF-7 CELL LINE; METABOLISM; PROTEIN FOLDING; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; X RAY CRYSTALLOGRAPHY;

ALLOSTERIC SITE; ANILINE COMPOUNDS; BENZYLIDENE COMPOUNDS; CATALYTIC DOMAIN; CELL MEMBRANE; CERAMIDES; CRYSTALLOGRAPHY, X-RAY; HUMANS; LIPIDS; MCF-7 CELLS; PROTEIN BINDING; PROTEIN FOLDING; SACCHAROMYCES CEREVISIAE; SIGNAL TRANSDUCTION; SPHINGOMYELIN PHOSPHODIESTERASE;

EID: 85023166064     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1705134114     Document Type: Article

References (71)

1. Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259: 1769-1771.
2. Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: Lessons from sphingolipids. Nat Rev Mol Cell Biol 9: 139-150.
3. Jenkins RW, Canals D, Hannun YA (2009) Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell Signal 21: 836-846.
4. Shamseddine AA, Airola MV, Hannun YA (2015) Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes. Adv Biol Regul 57: 24-41.
5. Xiong Z-J, Huang J, Poda G, Pomès R, Privé GG (2016) Structure of human acid sphingomyelinase reveals the role of the saposin domain in activating substrate hydrolysis. J Mol Biol 428: 3026-3042.
6. Gorelik A, Illes K, Heinz LX, Superti-Furga G, Nagar B (2016) Crystal structure of mammalian acid sphingomyelinase. Nat Commun 7: 12196.
7. Zhou Y-F, et al. (2016) Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease. Nat Commun 7: 13082.
8. Gorelik A, Liu F, Illes K, Nagar B (2017) Crystal structure of the human alkaline sphin-gomyelinase provides insights into substrate recognition. J Biol Chem 292: 7087-7094.
9. Kim M-Y, Linardic C, Obeid L, Hannun Y (1991) Identification of sphingomyelin turnover as an effector mechanism for the action of tumor necrosis factor alpha and gamma-interferon. Specific role in cell differentiation. J Biol Chem 266: 484-489.
10. Dressler KA, Mathias S, Kolesnick RN (1992) Tumor necrosis factor-alpha activates the sphingomyelin signal transduction pathway in a cell-free system. Science 255: 1715-1718.
11. Adam D, Wiegmann K, Adam-Klages S, Ruff A, Krönke M (1996) A novel cytoplasmic domain of the p55 tumor necrosis factor receptor initiates the neutral sphingomye-linase pathway. J Biol Chem 271: 14617-14622.
12. Adam-Klages S, et al. (1996) FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase. Cell 86: 937-947.
13. Belka C, et al. (1995) Tumor necrosis factor (TNF)-alpha activates c-raf-1 kinase via the p55 TNF receptor engaging neutral sphingomyelinase. EMBO J 14: 1156-1165.
14. Philipp S, et al. (2010) The Polycomb group protein EED couples TNF receptor 1 to neutral sphingomyelinase. Proc Natl Acad Sci USA 107: 1112-1117.
15. Clarke CJ, Cloessner EA, Roddy PL, Hannun YA (2011) Neutral sphingomyelinase 2 (nSMase2) is the primary neutral sphingomyelinase isoform activated by tumour necrosis factor-α in MCF-7 cells. Biochem J 435: 381-390.
16. Marchesini N, et al. (2004) Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth arrest of MCF7 cells. J Biol Chem 279: 25101-25111.
17. Hayashi Y, Kiyono T, Fujita M, Ishibashi M (1997) cca1 is required for formation of growth-arrested confluent monolayer of rat 3Y1 cells. J Biol Chem 272: 18082-18086.
18. Liu B, et al. (1998) Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-α-induced cell death. J Biol Chem 273: 11313-11320.
19. Barth BM, Gustafson SJ, Kuhn TB (2012) Neutral sphingomyelinase activation precedes NADPH oxidase-dependent damage in neurons exposed to the proin-flammatory cytokine tumor necrosis factor-α. J Neurosci Res 90: 229-242.
20. Rutkute K, Asmis RH, Nikolova-Karakashian MN (2007) Regulation of neutral sphin-gomyelinase-2 by GSH: A new insight to the role of oxidative stress in aging-associated inflammation. J Lipid Res 48: 2443-2452.
21. Karakashian AA, Giltiay NV, Smith GM, Nikolova-Karakashian MN (2004) Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-β-induced JNK activation. FASEB J 18: 968-970.
22. Luberto C, et al. (2002) Inhibition of tumor necrosis factor-induced cell death in MCF7 by a novel inhibitor of neutral sphingomyelinase. J Biol Chem 277: 41128-41139.
23. Hofmann K, Tomiuk S, Wolff G, Stoffel W (2000) Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc Natl Acad Sci USA 97: 5895-5900.
24. Marchesini N, Luberto C, Hannun YA (2003) Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism. J Biol Chem 278: 13775-13783.
25. Mittelbrunn M, et al. (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2: 282.
26. Montecalvo A, et al. (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119: 756-766.
27. Aubin I, et al. (2005) A deletion in the gene encoding sphingomyelin phosphodies-terase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nat Genet 37: 803-805.
28. Stoffel W, Jenke B, Blöck B, Zumbansen M, Koebke J (2005) Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development. Proc Natl Acad Sci USA 102: 4554-4559.
29. Khavandgar Z, et al. (2011) A cell-autonomous requirement for neutral sphingo-myelinase 2 in bone mineralization. J Cell Biol 194: 277-289.
30. Trajkovic K, et al. (2008) Ceramide triggers budding of exosome vesicles into multi-vesicular endosomes. Science 319: 1244-1247.
31. Kosaka N, et al. (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285: 17442-17452.
32. Tominaga N, et al. (2015) Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat Commun 6: 6716.
33. Kosaka N, et al. (2013) Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem 288: 10849-10859.
34. Asai H, et al. (2015) Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 18: 1584-1593.
35. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E (2014) Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging 35: 1792-1800.
36. Tani M, Hannun YA (2007) Analysis of membrane topology of neutral sphingomye-linase 2. FEBS Lett 581: 1323-1328.
37. Wu BX, et al. (2011) Identification of novel anionic phospholipid binding domains in neutral sphingomyelinase 2 with selective binding preference. J Biol Chem 286: 22362-22371.
38. Tomiuk S, Hofmann K, Nix M, Zumbansen M, Stoffel W (1998) Cloned mammalian neutral sphingomyelinase: Functions in sphingolipid signaling? Proc Natl Acad Sci USA 95: 3638-3643.
39. Airola MV, Hannun YA (2013) Sphingolipid metabolism and neutral sphingomyeli-nases. Sphingolipids: Basic Science and Drug Development (Springer, Vienna), pp 57-76.
40. Openshaw AE, Race PR, Monzó HJ, Vázquez-Boland J-A, Banfield MJ (2005) Crystal structure of SmcL, a bacterial neutral sphingomyelinase C from Listeria. J Biol Chem 280: 35011-35017.
41. Ago H, et al. (2006) Structural basis of the sphingomyelin phosphodiesterase activity in neutral sphingomyelinase from Bacillus cereus. J Biol Chem 281: 16157-16167.
42. Huseby M, et al. (2007) Structure and biological activities of beta toxin from Staph-ylococcus aureus. J Bacteriol 189: 8719-8726.
43. Filosto S, Ashfaq M, Chung S, Fry W, Goldkorn T (2012) Neutral sphingomyelinase 2 activity and protein stability are modulated by phosphorylation of five conserved serines. J Biol Chem 287: 514-522.
44. Filosto S, Fry W, Knowlton AA, Goldkorn T (2010) Neutral sphingomyelinase 2 (nSMase2) is a phosphoprotein regulated by calcineurin (PP2B). J Biol Chem 285: 10213-10222.
45. Kim WJ, et al. (2008) Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood 111: 4716-4722.
46. Hicks SN, et al. (2008) General and versatile autoinhibition of PLC isozymes. Mol Cell 31: 383-394.
47. Lyon AM, Begley JA, Manett TD, Tesmer JJG (2014) Molecular mechanisms of phospholipase C β3 autoinhibition. Structure 22: 1844-1854.
48. Milhas D, Clarke CJ, Idkowiak-Baldys J, Canals D, Hannun YA (2010) Anterograde and retrograde transport of neutral sphingomyelinase-2 between the Golgi and the plasma membrane. Biochim Biophys Acta 1801: 1361-1374.
49. Bernheimer AW (1974) Interactions between membranes and cytolytic bacterial toxins. Biochim Biophys Acta 344: 27-50.
50. Tani M, Hannun YA (2007) Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues. Role of palmitoylation in subcellular localization. J Biol Chem 282: 10047-10056.
51. Okamoto Y, Vaena de Avalos S, Hannun YA (2003) Functional analysis of ISC1 by site-directed mutagenesis. Biochemistry 42: 7855-7862.
52. Stagljar I, Korostensky C, Johnsson N, te Heesen S (1998) A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc Natl Acad Sci USA 95: 5187-5192.
53. Pavoine C, Pecker F (2009) Sphingomyelinases: Their regulation and roles in cardiovascular pathophysiology. Cardiovasc Res 82: 175-183.
54. Fairn GD, et al. (2011) High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine. J Cell Biol 194: 257-275.
55. Hannun YA (1996) Functions of ceramide in coordinating cellular responses to stress. Science 274: 1855-1859.
56. Guo BB, Bellingham SA, Hill AF (2015) The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes. J Biol Chem 290: 3455-3467.
57. Kabsch W (2010) XDS. Acta Crystallogr D Biol Crystallogr 66: 125-132.
58. Evans PR, Murshudov GN (2013) How good are my data and what is the resolution? Acta Crystallogr D Biol Crystallogr 69: 1204-1214.
59. Vonrhein C, et al. (2011) Data processing and analysis with the autoPROC toolbox. Acta Crystallogr D Biol Crystallogr 67: 293-302.
60. Schneider TR, Sheldrick GM (2002) Substructure solution with SHELXD. Acta Crystallogr D Biol Crystallogr 58: 1772-1779.
61. Dauter Z, Dauter M, Dodson E (2002) Jolly SAD. Acta Crystallogr D Biol Crystallogr 58: 494-506.
62. Vonrhein C, Blanc E, Roversi P, Bricogne G (2007) Automated structure solution with autoSHARP. Methods Mol Biol 364: 215-230.
63. Abrahams JP, Leslie AG (1996) Methods used in the structure determination of bovine mitochondrial F1 ATPase. Acta Crystallogr D Biol Crystallogr 52: 30-42.
64. Cowtan K (2006) The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr D Biol Crystallogr 62: 1002-1011.
65. Cowtan K (2010) Recent developments in classical density modification. Acta Crystallogr D Biol Crystallogr 66: 470-478.
66. McCoy AJ, et al. (2007) Phaser crystallographic software. J Appl Cryst 40: 658-674.
67. Emsley P, Lohkamp B, Scott WG, Cowtan K (2010) Features and development of Coot. Acta Crystallogr D Biol Crystallogr 66: 486-501.
68. Zwart P, et al. (2008) Automated structure solution with the PHENIX suite. Structural Proteomics, eds Kobe B, Guss M, Huber T (Springer, New York), Vol 426, pp 419-435.
69. Smart OS, et al. (2012) Exploiting structure similarity in refinement: Automated NCS and target-structure restraints in BUSTER. Acta Crystallogr D Biol Crystallogr 68: 368-380.
70. Chen VB, et al. (2010) MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66: 12-21.
71. Shamseddine AA, et al. (2015) P53-dependent upregulation of neutral sphingomyelinase-2: Role in doxorubicin-induced growth arrest. Cell Death Dis 6: e1947.