Protein O-fucosylation: structure and function

Current Opinion in Structural Biology

Volumn 56, Issue , 2019, Pages 78-86

  Holdener, Bernadette C ^a   Haltiwanger, Robert S ^b  

^a STONY BROOK UNIVERSITY   (United States)

^b UNIVERSITY OF GEORGIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPIDERMAL GROWTH FACTOR; FUCOSE; FUCOSYLTRANSFERASE; PROTEIN O FUCOSYLTRANSFERASE 1; PROTEIN O FUCOSYLTRANSFERASE 2; SUGAR; THROMBOSPONDIN 1; UNCLASSIFIED DRUG; GLYCOPROTEIN;

DISEASE ASSOCIATION; FUCOSYLATION; HUMAN; NOTCH SIGNALING; PREDICTION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CROSS LINKING; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; PROTEIN SECRETION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; CHEMISTRY; GLYCOSYLATION; METABOLISM; PHENOTYPE;

FUCOSE; GLYCOPROTEINS; GLYCOSYLATION; HUMANS; PHENOTYPE;

EID: 85060462431     PISSN: 0959440X     EISSN: 1879033X     Source Type: Journal    
DOI: 10.1016/j.sbi.2018.12.005     Document Type: Review

References (74)

1. Schneider, M., Al-Shareffi, E., Haltiwanger, R.S., Biological functions of fucose in mammals. Glycobiology 27 (2017), 601–618.
2. Varshney, S., Stanley, P., Multiple roles for O-glycans in Notch signalling. FEBS Lett 592 (2018), 3819–3834 Excellent, recent comprehensive review of O-glycans occurring on the Notch receptor.
3. Haltom, A.R., Jafar-Nejad, H., The multiple roles of epidermal growth factor repeat O-glycans in animal development. Glycobiology 25 (2015), 1027–1042.
4. Vasudevan, D., Haltiwanger, R.S., Novel roles for O-linked glycans in protein folding. Glycoconj J 31 (2014), 417–426.
5. Swearingen, K.E., Lindner, S.E., Shi, L., Shears, M.J., Harupa, A., Hopp, C.S., Vaughan, A.M., Springer, T.A., Moritz, R.L., Kappe, S.H., et al. Interrogating the plasmodium sporozoite surface: identification of surface-exposed proteins and demonstration of glycosylation on CSP and TRAP by mass spectrometry-based proteomics. PLoS Pathog, 12, 2016, e1005606.
6. Lopaticki, S., Yang, A.S.P., John, A., Scott, N.E., Lingford, J.P., O'Neill, M.T., Erickson, S.M., McKenzie, N.C., Jennison, C., Whitehead, L.W., et al. Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts. Nat Commun, 8, 2017, 561 Presents evidence for thein vivo importance of POFUT2 in localization and function of the TRAP protein in Plasmodium.
7. Bandini, G., Leon, D.R., Hoppe, C.M., Zhang, Y., Agop-Nersesian, C., Shears, M.J., Mahal, L.K., Routier, F.H., Costello, C.E., Samuelson, J., O-Fucosylation of thrombospondin-like repeats is required for processing of microneme protein 2 and for efficient host cell invasion by Toxoplasma gondii tachyzoites. J Biol Chem, 2018 (in press) Consistent with Ref. 6, presents evidence for thein vivo importance of POFUT2 in processing and function of the MIC2 protein in Toxoplasma.
8. Khurana, S., Coffey, M.J., John, A., Uboldi, A.D., Huynh, M.H., Stewart, R.J., Carruthers, V., Tonkin, C.J., Goddard-Borger, E.D., Scott, N.E., Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection. J Biol Chem, 2018 in press)In contrast to Ref. 7, shows a less significant effect of eliminating POFUT2 in Toxoplasma.
9. Gas-Pascual, E., Ichikawa, H.T., Sheikh, M.O., Serji, M.I., Deng, B., Mandalasi, M., Bandini, G., Samuelson, J., Wells, L., West, C.M., CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology. J Biol Chem, 2018 (in press).
10. Zentella, R., Sui, N., Barnhill, B., Hsieh, W.P., Hu, J., Shabanowitz, J., Boyce, M., Olszewski, N.E., Zhou, P., Hunt, D.F., et al. The Arabidopsis O-fucosyltransferase SPINDLY activates nuclear growth repressor DELLA. Nat Chem Biol 13 (2017), 479–485.
11. Bandini, G., Haserick, J.R., Motari, E., Ouologuem, D.T., Lourido, S., Roos, D.S., Costello, C.E., Robbins, P.W., Samuelson, J., O-Fucosylated glycoproteins form assemblies in close proximity to the nuclear pore complexes of Toxoplasma gondii. Proc Natl Acad Sci U S A 113 (2016), 11567–11572.
12. Wang, Y., Lee, G.F., Kelley, R.F., Spellman, M.W., Identification of a GDP-L-fucose: polypeptide fucosyltransferase and enzymatic addition of O-linked fucose to EGF domains. Glycobiology 6 (1996), 837–842.
13. Luo, Y., Nita-Lazar, A., Haltiwanger, R.S., Two distinct pathways for O-fucosylation of epidermal growth factor-like or thrombospondin type 1 repeats. J Biol Chem 281 (2006), 9385–9392.
14. Valero-Gonzalez, J., Leonhard-Melief, C., Lira-Navarrete, E., Jimenez-Oses, G., Hernandez-Ruiz, C., Pallares, M.C., Yruela, I., Vasudevan, D., Lostao, A., Corzana, F., et al. A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2. Nat Chem Biol 12 (2016), 240–246 Structure of POFUT2 in complex with a TSR showing how it recognizes a folded TSR and orients it for catalysis.
15. Li, Z., Han, K., Pak, J.E., Satkunarajah, M., Zhou, D., Rini, J.M., Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1. Nat Chem Biol 13 (2017), 757–763 Structures of POFUT1 in complex with EGF repeats showing how the enzyme recognizes a folded EGF repeat and orients it in the binding pocket for catalysis.
16. Smith, D.K., Harper, J.F., Wallace, I.S., A potential role for protein O-fucosylation during pollen-pistil interactions. Plant Signal Behav, 13, 2018, e1467687.
17. Vasudevan, D., Takeuchi, H., Johar, S.S., Majerus, E., Haltiwanger, R.S., Peters plus syndrome mutations disrupt a Noncanonical ER quality-control mechanism. Curr Biol 25 (2015), 286–295 First description of how POFUT2 and B3GLCT function in a non-canonical ER quality control pathway for folding of TSRs by stabilization.
18. Takeuchi, H., Yu, H., Hao, H., Takeuchi, M., Ito, A., Li, H., Haltiwanger, R.S., O-Glycosylation modulates the stability of epidermal growth factor-like repeats and thereby regulates Notch trafficking. J Biol Chem 292 (2017), 15964–15973 This study demonstrates how POFUT1 functions in a non-canonical ER quality control pathway for folding of EGF repeats by stabilization.
19. Shi, S., Stanley, P., Protein O-fucosyltransferase I is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A 100 (2003), 5234–5239.
20. Okajima, T., Irvine, K.D., Regulation of notch signaling by O-linked fucose. Cell 111 (2002), 893–904.
21. Kim, M.L., Chandrasekharan, K., Glass, M., Shi, S., Stahl, M.C., Kaspar, B., Stanley, P., Martin, P.T., O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors. Mol Cell Neurosci 39 (2008), 452–464.
22. Serth, K., Schuster-Gossler, K., Kremmer, E., Hansen, B., Marohn-Kohn, B., Gossler, A., O-Fucosylation of DLL3 is required for its function during Somitogenesis. PLoS One, 10, 2015, e0123776.
23. Moloney, D.J., Panin, V.M., Johnston, S.H., Chen, J., Shao, L., Wilson, R., Wang, Y., Stanley, P., Irvine, K.D., Haltiwanger, R.S., et al. Fringe is a Glycosyltransferase that modifies Notch. Nature 406 (2000), 369–375.
24. Johnston, S.H., Rauskolb, C., Wilson, R., Prabhakaran, B., Irvine, K.D., Vogt, T.F., A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway. Development 124 (1997), 2245–2254.
25. Panin, V.M., Papayannopoulos, V., Wilson, R., Irvine, K.D., Fringe modulates notch ligand interactions. Nature 387 (1997), 908–912.
26. Kakuda, S., Haltiwanger, R.S., Deciphering the fringe-mediated notch code: identification of activating and inhibiting sites allowing discrimination between ligands. Dev Cell 40 (2017), 193–201 Mapped sites of O-fucose and Fringe modification on mouse NOTCH1, and examined which sites are important for Fringe to modulate NOTCH1 function. Note that Fringe enzymes were overexpressed in a Fringe-deficient background in these studies.
27. LeBon, L., Lee, T.V., Sprinzak, D., Jafar-Nejad, H., Elowitz, M.B., Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states. Elife, 3, 2014, e02950.
28. Luo, Y., Koles, K., Vorndam, W., Haltiwanger, R.S., Panin, V.M., Protein O-fucosyltransferase 2 adds O-fucose to thrombospondin type 1 repeats. J Biol Chem 281 (2006), 9393–9399.
29. Kozma, K., Keusch, J.J., Hegemann, B., Luther, K.B., Klein, D., Hess, D., Haltiwanger, R.S., Hofsteenge, J., Identification and characterization of a beta1,3-glucosyltransferase that synthesizes the Glc-beta1,3-Fuc disaccharide on thrombospondin type 1 repeats. J Biol Chem 281 (2006), 36742–36751.
30. Sato, T., Sato, M., Kiyohara, K., Sogabe, M., Shikanai, T., Kikuchi, N., Togayachi, A., Ishida, H., Ito, H., Kameyama, A., et al. Molecular cloning and characterization of a novel human beta1,3-glucosyltransferase, which is localized at the endoplasmic reticulum and glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domain. Glycobiology 16 (2006), 1194–1206.
31. Li, M., Cheng, R., Liang, J., Yan, H., Zhang, H., Yang, L., Li, C., Jiao, Q., Lu, Z., He, J., et al. Mutations in POFUT1, encoding protein O-fucosyltransferase 1, cause generalized Dowling-Degos disease. Am J Hum Genet 92 (2013), 895–903.
32. Du, Y., Li, D., Li, N., Su, C., Yang, C., Lin, C., Chen, M., Wu, R., Li, X., Hu, G., POFUT1 promotes colorectal cancer development through the activation of Notch1 signaling. Cell Death Dis, 9, 2018, 995.
33. Ma, L., Dong, P., Liu, L., Gao, Q., Duan, M., Zhang, S., Chen, S., Xue, R., Wang, X., Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. Biochem Biophys Res Commun 473 (2016), 503–510.
34. Du, J., Takeuchi, H., Leonhard-Melief, C., Shroyer, K.R., Dlugosz, M., Haltiwanger, R.S., Holdener, B.C., O-Fucosylation of thrombospondin type 1 repeats restricts epithelial to mesenchymal transition (EMT) and maintains epiblast pluripotency during mouse gastrulation. Dev Biol 346 (2010), 25–38.
35. Benz, B.A., Nandadasa, S., Takeuchi, M., Grady, R.C., Takeuchi, H., LoPilato, R.K., Kakuda, S., Somerville, R.P., Apte, S.S., Haltiwanger, R.S., et al. Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. Dev Biol 416 (2016), 111–122 Demonstration that early embryonic phenotypes of Pofut2-null mice are likely due to loss of ADAMTS9 function.
36. Sparrow, D.B., Chapman, G., Wouters, M.A., Whittock, N.V., Ellard, S., Fatkin, D., Turnpenny, P.D., Kusumi, K., Sillence, D., Dunwoodie, S.L., Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype. Am J Hum Genet 78 (2006), 28–37.
37. Zhang, N., Gridley, T., Defects in somite formation in lunatic fringe-deficient mice. Nature 394 (1998), 374–377.
38. Evrard, Y.A., Lun, Y., Aulehla, A., Gan, L., Johnson, R.L., Lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 394 (1998), 377–381.
39. Xu, K., Nieuwenhuis, E., Cohen, B.L., Wang, W., Canty, A.J., Danska, J.S., Coultas, L., Rossant, J., Wu, M.Y., Piscione, T.D., et al. Lunatic fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol 298 (2010), L45–L56.
40. Hahn, K.L., Johnson, J., Beres, B.J., Howard, S., Wilson-Rawls, J., Lunatic fringe null female mice are infertile due to defects in meiotic maturation. Development 132 (2005), 817–828.
41. Song, Y., Kumar, V., Wei, H.X., Qiu, J., Stanley, P., Lunatic, manic, and radical fringe each promote T and B Cell development. J Immunol 196 (2016), 232–243.
42. Benedito, R., Roca, C., Sorensen, I., Adams, S., Gossler, A., Fruttiger, M., Adams, R.H., The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 137 (2009), 1124–1135.
43. Moran, J.L., Shifley, E.T., Levorse, J.M., Mani, S., Ostmann, K., Perez-Balaguer, A., Walker, D.M., Vogt, T.F., Cole, S.E., Manic fringe is not required for embryonic development, and fringe family members do not exhibit redundant functions in the axial skeleton, limb, or hindbrain. Dev Dyn 238 (2009), 1803–1812.
44. D'Amato, G., Luxan, G., Del Monte-Nieto, G., Martinez-Poveda, B., Torroja, C., Walter, W., Bochter, M.S., Benedito, R., Cole, S., Martinez, F., et al. Sequential Notch activation regulates ventricular chamber development. Nat Cell Biol 18 (2016), 7–20.
45. Zhang, S., Chung, W.C., Wu, G., Egan, S.E., Miele, L., Xu, K., Manic Fringe promotes a claudin-low breast cancer phenotype through Notch-mediated PIK3CG induction. Cancer Res 75 (2015), 1936–1943.
46. Zhang, S., Chung, W.C., Xu, K., Lunatic Fringe is a potent tumor suppressor in Kras-initiated pancreatic cancer. Oncogene 35 (2016), 2485–2495.
47. Lesnik Oberstein, S.A., Kriek, M., White, S.J., Kalf, M.E., Szuhai, K., den Dunnen, J.T., Breuning, M.H., Hennekam, R.C., Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet 79 (2006), 562–566.
48. Weh, E., Reis, L.M., Tyler, R.C., Bick, D., Rhead, W.J., Wallace, S., McGregor, T.L., Dills, S.K., Chao, M.C., Murray, J.C., et al. Novel B3GALTL mutations in classic peters plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes. Clin Genet 86 (2014), 142–148.
49. Dubail, J., Vasudevan, D., Wang, L.W., Earp, S.E., Jenkins, M.W., Haltiwanger, R.S., Apte, S.S., Impaired ADAMTS9 secretion: a potential mechanism for eye defects in Peters Plus Syndrome. Sci Rep, 6, 2016, 33974.
50. Harvey, B.M., Rana, N.A., Moss, H., Leonardi, J., Jafar-Nejad, H., Haltiwanger, R.S., Mapping sites of O-glycosylation and fringe elongation on Drosophila Notch. J Biol Chem 291 (2016), 16348–16360.
51. Rampal, R., Li, A.S., Moloney, D.J., Georgiou, S.A., Luther, K.B., Nita-Lazar, A., Haltiwanger, R.S., Lunatic fringe, manic fringe, and radical fringe recognize similar specificity determinants in O-fucosylated epidermal growth factor-like repeats. J Biol Chem 280 (2005), 42454–42463.
52. Luca, V.C., Jude, K.M., Pierce, N.W., Nachury, M.V., Fischer, S., Garcia, K.C., Structural basis for Notch1 engagement of Delta-like 4. Science 347 (2015), 847–853 Together with Ref. 53, shows that O-fucose on Notch EGF repeats directly participate in ligand interactions. Note that the structures were obtained after directed evolution of the ligand toward stronger affinities.
53. Luca, V.C., Kim, B.C., Ge, C., Kakuda, S., Wu, D., Roein-Peikar, M., Haltiwanger, R.S., Zhu, C., Ha, T., Garcia, K.C., Notch-Jagged complex structure implicates a catch bond in tuning ligand sensitivity. Science 355 (2017), 1320–1324 Together with Ref. 52, shows that O-fucose on Notch EGF repeats directly participate in ligand interactions. Note that the structures were obtained after directed evolution of the ligand toward stronger affinities.
54. Ge, C., Stanley, P., The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development. Proc Natl Acad Sci U S A 105 (2008), 1539–1544.
55. Taylor, P., Takeuchi, H., Sheppard, D., Chillakuri, C., Lea, S.M., Haltiwanger, R.S., Handford, P.A., Fringe-mediated extension of O-linked fucose in the ligand-binding region of Notch1 increases binding to mammalian Notch ligands. Proc Natl Acad Sci U S A 111 (2014), 7290–7295.
56. Gordon, W.R., Zimmerman, B., He, L., Miles, L.J., Huang, J., Tiyanont, K., McArthur, D.G., Aster, J.C., Perrimon, N., Loparo, J.J., et al. Mechanical allostery: evidence for a force requirement in the proteolytic activation of Notch. Dev Cell 33 (2015), 729–736.
57. Adams, J.C., Tucker, R.P., The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Develop Dyn 218 (2000), 280–299.
58. Xu, C., Ng, D.T., Glycosylation-directed quality control of protein folding. Nat Rev Mol Cell Biol 16 (2015), 742–752.
59. Luo, Y., Haltiwanger, R.S., O-fucosylation of Notch occurs in the endoplasmic reticulum. J Biol Chem 280 (2005), 11289–11294.
60. Munro, S., Freeman, M., The notch signalling regulator fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. Curr Biol 10 (2000), 813–820.
61. Hicks, C., Johnston, S.H., DiSibio, G., Collazo, A., Vogt, T.F., Weinmaster, G., Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2. Nat Cell Biol 2 (2000), 515–520.
62. Okajima, T., Xu, A., Lei, L., Irvine, K.D., Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding. Science 307 (2005), 1599–1603.
63. Ajima, R., Suzuki, E., Saga, Y., Pofut1 point-mutations that disrupt O-fucosyltransferase activity destabilize the protein and abolish Notch1 signaling during mouse somitogenesis. PLoS One, 12, 2017, e0187248.
64. McMillan, B.J., Zimmerman, B., Egan, E.D., Lofgren, M., Xu, X., Hesser, A., Blacklow, S.C., Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations. Glycobiology, 2017, 1–10.
65. Ishio, A., Sasamura, T., Ayukawa, T., Kuroda, J., Ishikawa, H.O., Aoyama, N., Matsumoto, K., Gushiken, T., Okajima, T., Yamakawa, T., et al. O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation. J Biol Chem 290 (2015), 505–519.
66. Yao, D., Huang, Y., Huang, X., Wang, W., Yan, Q., Wei, L., Xin, W., Gerson, S., Stanley, P., Lowe, J.B., et al. Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions. Blood 117 (2011), 5652–5662.
67. Stahl, M., Uemura, K., Ge, C., Shi, S., Tashima, Y., Stanley, P., Roles of Pofut1 and O-fucose in mammalian Notch signaling. J Biol Chem 283 (2008), 13638–13651.
68. Hubmacher, D., Schneider, M., Berardinelli, S.J., Takeuchi, H., Willard, B., Reinhardt, D.P., Haltiwanger, R.S., Apte, S.S., Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease. Sci Rep, 7, 2017, 41871.
69. Morales, J., Al-Sharif, L., Khalil, D.S., Shinwari, J.M., Bavi, P., Al-Mahrouqi, R.A., Al-Rajhi, A., Alkuraya, F.S., Meyer, B.F., Al Tassan, N., Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. Am J Hum Genet 85 (2009), 558–568.
70. Le Goff, C., Morice-Picard, F., Dagoneau, N., Wang, L.W., Perrot, C., Crow, Y.J., Bauer, F., Flori, E., Prost-Squarcioni, C., Krakow, D., et al. ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet 40 (2008), 1119–1123.
71. Kelwick, R., Desanlis, I., Wheeler, G.N., Edwards, D.R., The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome Biol, 16, 2015, 113.
72. Kadur Lakshminarasimha Murthy, P., Srinivasan, T., Bochter, M.S., Xi, R., Varanko, A.K., Tung, K.L., Semerci, F., Xu, K., Maletic-Savatic, M., Cole, S.E., et al. Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis. Elife, 7, 2018.
73. Davis, I.W., Leaver-Fay, A., Chen, V.B., Block, J.N., Kapral, G.J., Wang, X., Murray, L.W., Arendall, W.B. 3rd, Snoeyink, J., Richardson, J.S., et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res 35 (2007), W375–W383.
74. Chen, V.B., Arendall, W.B. 3rd, Headd, J.J., Keedy, D.A., Immormino, R.M., Kapral, G.J., Murray, L.W., Richardson, J.S., Richardson, D.C., MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66 (2010), 12–21.