Intramembrane Proteolysis: Theme and Variations
10.1126/science.1096187
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Proteases that reside in cellular membranes apparently wield water to hydrolyze the peptide bonds of substrates despite their water-excluding environment. Although these intramembrane proteases bear little or no sequence resemblance to classical water-soluble proteases, they have ostensibly converged on similar hydrolytic mechanisms. Identification of essential amino acid residues of these proteases suggests that they use residue combinations for catalysis in the same way as their soluble cousins. In contrast to classical proteases, however, the catalytic residues of intramembrane proteases lie within predicted hydrophobic transmembrane domains. Elucidating the biological functions of intramembrane proteases, identifying their substrates, and understanding how they hydrolyze peptide bonds within membranes will shed light on the ways these proteases regulate crucial biological processes and contribute to disease.

Bibliography

Wolfe, M. S., & Kopan, R. (2004). Intramembrane Proteolysis: Theme and Variations. Science, 305(5687), 1119–1123.

Authors 2
  1. Michael S. Wolfe (first)
  2. Raphael Kopan (additional)
References 75 Referenced 287
  1. A. J. Barrett J. F. Woessner N. D. Rawlings Eds. Handbook of Proteolytic Enzymes (Academic Press New York 1998).
  2. M. S. Wolfe, J. De Los Angeles, D. D. Miller, W. Xia, D. J. Selkoe, Biochemistry38, 11223 (1999). (10.1021/bi991080q) / Biochemistry (1999)
  3. 10.1016/S0092-8674(00)80213-5
  4. A. Nohturfft, R. A. DeBose-Boyd, S. Scheek, J. L. Goldstein, M. S. Brown, Proc. Natl. Acad. Sci. U.S.A.96, 11235 (1999). (10.1073/pnas.96.20.11235) / Proc. Natl. Acad. Sci. U.S.A. (1999)
  5. R. B. Rawson, Nature Rev. Mol. Cell Biol.4, 631 (2003). (10.1038/nrm1174) / Nature Rev. Mol. Cell Biol. (2003)
  6. 10.1016/S1097-2765(00)80150-1
  7. 10.1074/jbc.273.28.17801
  8. 10.1016/S1097-2765(00)80006-4
  9. N. G. Zelenski, R. B. Rawson, M. S. Brown, J. L. Goldstein, J. Biol. Chem.274, 21973 (1999). (10.1074/jbc.274.31.21973) / J. Biol. Chem. (1999)
  10. 10.1073/pnas.96.26.14765
  11. K. Kanehara, Y. Akiyama, K. Ito, Gene281, 71 (2001). (10.1016/S0378-1119(01)00823-X) / Gene (2001)
  12. J. Ye, U. P. Dave, N. V. Grishin, J. L. Goldstein, M. S. Brown, Proc. Natl. Acad. Sci. U.S.A.97, 5123 (2000). (10.1073/pnas.97.10.5123) / Proc. Natl. Acad. Sci. U.S.A. (2000)
  13. 10.1126/science.1072994
  14. 10.1038/34910
  15. 10.1021/bi982562p
  16. 10.1038/19077
  17. G. Thinakaranet al., J. Biol. Chem.272, 28415 (1997). (10.1074/jbc.272.45.28415) / J. Biol. Chem. (1997)
  18. 10.1074/jbc.273.26.16470
  19. 10.1074/jbc.273.6.3205
  20. J. Zhanget al., J. Biol. Chem.273, 12436 (1998). (10.1074/jbc.273.20.12436) / J. Biol. Chem. (1998)
  21. H. Laudonet al., J. Neurochem.89, 44 (2004). (10.1046/j.1471-4159.2003.02298.x) / J. Neurochem. (2004)
  22. 10.1038/35015085
  23. 10.1038/35017062
  24. 10.1038/377351a0
  25. 10.1126/science.284.5415.770
  26. 10.1073/pnas.95.14.8108
  27. 10.1016/S1097-2765(00)80417-7
  28. 10.1016/S1097-2765(00)80416-5
  29. 10.1038/19083
  30. 10.1038/30756
  31. 10.1038/35016111
  32. 10.1126/science.1058783
  33. X. Cao, T. C. Sudhof, J. Biol. Chem., 279, 24601 (2004). (10.1074/jbc.M402248200) / J. Biol. Chem. (2004)
  34. C. Goutte, W. Hepler, K. M. Mickey, J. R. Priess, Development127, 2481 (2000). (10.1242/dev.127.11.2481) / Development (2000)
  35. 10.1016/S1534-5807(02)00189-2
  36. 10.1073/pnas.022523499
  37. 10.1038/35024009
  38. H. M. Chung, G. Struhl, Nature Cell Biol.3, 1129 (2001). (10.1038/ncb1201-1129) / Nature Cell Biol. (2001)
  39. 10.1038/nature01506
  40. 10.1073/pnas.1037392100
  41. 10.1073/pnas.052436599
  42. 10.1038/ncb960
  43. M. J. LaVoieet al., J. Biol. Chem.278, 37213 (2003). (10.1074/jbc.M303941200) / J. Biol. Chem. (2003)
  44. 10.1083/jcb.200304014
  45. P. C. Fraeringet al., Biochemistry43, 323 (2004). (10.1021/bi035748j) / Biochemistry (2004)
  46. S. Prokop, K. Shirotani, D. Edbauer, C. Haass, H. Steiner, J. Biol. Chem.279, 23255 (2004). (10.1074/jbc.M401789200) / J. Biol. Chem. (2004)
  47. 10.1016/S0896-6273(03)00205-8
  48. P. Marambaudet al., Cell114, 635 (2003). / Cell (2003)
  49. O. Berezovska, P. Ramdya, M. S. Wolfe, B. Bacskai, B. T. Hyman, J. Neurosci.23, 4560 (2003). (10.1523/JNEUROSCI.23-11-04560.2003) / J. Neurosci. (2003)
  50. C. Daset al., J. Am. Chem. Soc.125, 11794 (2003). (10.1021/ja037131v) / J. Am. Chem. Soc. (2003)
  51. A. Y. Kornilova, C. Das, M. S. Wolfe, J. Biol. Chem.278, 16470 (2003). (10.1074/jbc.C300019200) / J. Biol. Chem. (2003)
  52. W. G. Annaertet al., Neuron32, 579 (2001). (10.1016/S0896-6273(01)00512-8) / Neuron (2001)
  53. E. H. Schroeteret al., Proc. Natl. Acad. Sci. U.S.A.100, 13075 (2003). (10.1073/pnas.1735338100) / Proc. Natl. Acad. Sci. U.S.A. (2003)
  54. 10.1073/pnas.110126897
  55. 10.1074/jbc.C200469200
  56. 10.1074/jbc.M211992200
  57. 10.1074/jbc.M306957200
  58. M. K. Lemberg, F. A. Bland, A. Weihofen, V. M. Braud, B. Martoglio, J. Immunol.167, 6441 (2001). (10.4049/jimmunol.167.11.6441) / J. Immunol. (2001)
  59. 10.1093/emboj/cdf414
  60. 10.1126/science.1070925
  61. 10.1093/hmg/11.9.1037
  62. A. Weihofenet al., J. Biol. Chem.278, 16528 (2003). (10.1074/jbc.M301372200) / J. Biol. Chem. (2003)
  63. A. C. Nyborget al., J. Biol. Chem.279, 15153 (2004). (10.1074/jbc.M309305200) / J. Biol. Chem. (2004)
  64. T. Golde personal communication.
  65. 10.1016/S1097-2765(02)00655-X
  66. J. R. Lee, S. Urban, C. F. Garvey, M. Freeman, Cell107, 161 (2001). (10.1016/S0092-8674(01)00526-8) / Cell (2001)
  67. 10.1016/S0092-8674(01)00525-6
  68. 10.1016/S1097-2765(03)00181-3
  69. S. Urban, D. Schlieper, M. Freeman, Curr. Biol.12, 1507 (2002). (10.1016/S0960-9822(02)01092-8) / Curr. Biol. (2002)
  70. 10.1016/S0022-2836(02)01000-8
  71. G. A. McQuibban, S. Saurya, M. Freeman, Nature423, 537 (2003). (10.1038/nature01633) / Nature (2003)
  72. M. Herlan, F. Vogel, C. Bornhovd, W. Neupert, A. S. Reichert, J. Biol. Chem.278, 27781 (2003). (10.1074/jbc.M211311200) / J. Biol. Chem. (2003)
  73. O. Loh, S. Urban, M. Freeman, Curr. Biol.14, 236 (2004). / Curr. Biol. (2004)
  74. Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
  75. We thank S. Urban for helpful comments on the manuscript. Supported by NIH and the Alzheimer's Association.
Dates
Type When
Created 21 years ago (Aug. 20, 2004, 1:58 p.m.)
Deposited 1 year, 7 months ago (Jan. 9, 2024, 10:30 p.m.)
Indexed 4 months, 1 week ago (April 18, 2025, 11:44 a.m.)
Issued 21 years ago (Aug. 20, 2004)
Published 21 years ago (Aug. 20, 2004)
Published Print 21 years ago (Aug. 20, 2004)
Funders 0

None

@article{Wolfe_2004, title={Intramembrane Proteolysis: Theme and Variations}, volume={305}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1096187}, DOI={10.1126/science.1096187}, number={5687}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wolfe, Michael S. and Kopan, Raphael}, year={2004}, month=aug, pages={1119–1123} }