Crossref journal-article
Wiley
Protein Science (311)
Abstract

AbstractCalmodulin and other members of the EF‐hand protein family are known to undergo major changes in conformation upon binding Ca2+. However, some EF‐hand proteins, such as calbindin D9k, bind Ca2+ without a significant change in conformation. Here, we show the importance of a precise balance of solvation energetics to conformational change, using mutational analysis of partially buried polar groups in the N‐terminal domain of calmodulin (N‐cam). Several variants were characterized using fluorescence, circular dichroism, and NMR spectroscopy. Strikingly, the replacement of polar side chains glutamine and lysine at positions 41 and 75 with nonpolar side chains leads to dramatic enhancement of the stability of the Ca2+‐free state, a corresponding decrease in Ca2+‐binding affinity, and an apparent loss of ability to change conformation to the open form. The results suggest a paradigm for conformational change in which energetic strain is accumulated in one state in order to modulate the energetics of change to the alternative state.

Bibliography

Ababou, A., & Desjarlais, J. R. (2001). Solvation energetics and conformational change in EF‐hand proteins. Protein Science, 10(2), 301–312. Portico.

Authors 2
  1. Abdessamad Ababou (first)
  2. John R. Desjarlais (additional)
References 59 Referenced 41
  1. 10.1126/science.1553532
  2. 10.1016/0022-2836(88)90608-0
  3. 10.1016/0006-291X(84)91431-1
  4. 10.1021/bi9800449
  5. 10.1021/bi00093a013
  6. 10.1038/371037a0
  7. 10.1016/S0959-440X(98)80101-2
  8. 10.1016/0022-2836(92)90324-D
  9. 10.1038/nsb0995-707
  10. 10.1021/bi00113a006
  11. 10.1007/BF00197809
  12. 10.1016/S0968-0004(99)01445-0
  13. 10.1021/bi9612226
  14. 10.1021/bi972635p
  15. 10.1021/bi9908235 / NMR solution structure of a complex of calmodulin with a binding peptide of the Ca2+ pump by Elshorst B. (1999)
  16. 10.1021/bi9628275
  17. 10.1021/bi9806448
  18. 10.1016/0092-8674(93)90491-8
  19. 10.1021/bi963076
  20. 10.1038/nsb0995-784
  21. 10.1038/nsb1296-1011
  22. 10.1016/S0021-9258(20)79739-5 / J. Biol. Chem. / Urea and guanidine hydrochloride denaturation of ribonuclease, lysozyme, alpha‐chymotrypsin, and beta‐lactoglobulin by Greene R.F. (1974)
  23. 10.1021/bi9605191
  24. 10.1038/313653a0
  25. 10.1146/annurev.bb.24.060195.000505
  26. 10.1016/S0968-0004(06)80021-6
  27. 10.1016/0006-2952(90)90190-V
  28. 10.1021/bi00102a013
  29. 10.1021/bi972642d
  30. 10.1006/jmbi.1993.1322
  31. 10.1107/S0021889891004399
  32. 10.1038/nsb0995-768
  33. 10.1016/S0021-9258(18)92938-8
  34. 10.1021/bi00215a023
  35. 10.1021/bi00027a013
  36. 10.1016/0006-291X(83)91093-8
  37. 10.1110/ps.9.8.1519
  38. 10.1016/S0076-6879(97)77028-9
  39. 10.1074/jbc.271.19.11284
  40. 10.1002/pro.5560070206
  41. 10.1023/A:1009253808876
  42. 10.1016/0076-6879(86)31045-0
  43. 10.1007/BF02192855
  44. 10.1016/S0065-3233(08)60460-X
  45. 10.1110/ps.9.6.1106
  46. 10.1002/pro.5560061002
  47. 10.1016/S0969-2126(98)00023-9
  48. 10.1042/bst0150772
  49. 10.1038/nsb0494-239
  50. 10.1006/jmbi.1995.0308
  51. 10.1021/bi00049a010
  52. 10.1021/bi9718200
  53. 10.1016/0022-2836(91)80195-Z
  54. 10.1016/0022-2836(92)90976-Q
  55. 10.1038/nsb0295-122
  56. 10.1007/BF00211777
  57. 10.1110/ps.8.9.1752
  58. 10.1073/pnas.94.8.3673
  59. 10.1038/nsb0995-758
Dates
Type When
Created 23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited 1 year, 10 months ago (Oct. 7, 2023, 3:11 a.m.)
Indexed 40 minutes ago (Aug. 29, 2025, 6:30 a.m.)
Issued 24 years, 6 months ago (Feb. 1, 2001)
Published 24 years, 6 months ago (Feb. 1, 2001)
Published Online 16 years, 7 months ago (Dec. 31, 2008)
Published Print 24 years, 6 months ago (Feb. 1, 2001)
Funders 0

None

@article{Ababou_2001, title={Solvation energetics and conformational change in EF‐hand proteins}, volume={10}, ISSN={1469-896X}, url={http://dx.doi.org/10.1110/ps.33601}, DOI={10.1110/ps.33601}, number={2}, journal={Protein Science}, publisher={Wiley}, author={Ababou, Abdessamad and Desjarlais, John R.}, year={2001}, month=feb, pages={301–312} }