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From crystal clear ligand binding to designer I domains

A long awaited crystal structure of an integrin I domain in complex with a peptide derived from collagen has revealed the ligand-bound conformation of this domain and suggests a mechanism for allosteric control of integrin function by ligand binding. Also, a computational protein design approach has allowed the creation of stable, high affinity forms of the I domain for the first time.

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Figure 1: Schematic view of the changes in metal ion coordination of the α2 I domain MIDAS motif upon ligand binding.
Figure 2: Open and closed conformations of the α2 and Mac-1 I domains.
Figure 3: Schematic diagram of integrin domain structure and hypothetical model of integrin allostery1,23,26,27,28,29,30.

References

  1. Emsley, J., Knight, C.G., Farndale, R.W., Barnes, M.J. & Liddington, R.C. Cell 101, 47–56 (2000).

    Article  CAS  Google Scholar 

  2. Shimaoka, M., Shifman, J.M., Takagi, J., Mayo, S.L. & Springer, T.A. Nature Struct. Biol. 7, 674–678 (2000).

    Article  CAS  Google Scholar 

  3. Springer, T.A. Proc. Natl. Acad. Sci. USA 94, 65–72 (1997).

    Article  CAS  Google Scholar 

  4. Michishita, M., Videm, V. & Arnaout, M.A. Cell 72, 857–867 (1993).

    Article  CAS  Google Scholar 

  5. Lee, J.-O., Rieu, P., Arnaout, M.A. & Liddington, R. Cell 80, 631–638 (1995).

    Article  CAS  Google Scholar 

  6. Lambright, D.G., Noel, J.P., Hamm, H.E. & Sigler, P.B. Nature 369, 621–628 (1994).

    Article  CAS  Google Scholar 

  7. Lee, J.-O., Bankston, L.A., Arnaout, M.A. & Liddington, R.C. Structure 3, 1333–1340 (1995).

    Article  CAS  Google Scholar 

  8. Qu, A. & Leahy, D.J. Proc. Natl. Acad. Sci. USA 92, 10277–10281 (1995).

    Article  CAS  Google Scholar 

  9. Qu, A. & Leahy, D.J. Structure 4, 931–942 (1996).

    Article  CAS  Google Scholar 

  10. Emsley, J., King, S.L., Bergelson, J.M. & Liddington, R.C. J. Biol. Chem. 272, 28512–28517 (1997).

    Article  CAS  Google Scholar 

  11. Rich, R.L. et al. J. Biol. Chem. 274, 24906–24913 (1999).

    Article  CAS  Google Scholar 

  12. Baldwin, E.T. et al. Structure 6, 923–935 (1998).

    Article  CAS  Google Scholar 

  13. Li, R., Rieu, P., Griffith, D.L., Scott, D. & Arnaout, M.A. J. Cell Biol. 143, 1523–1534 (1998).

    Article  CAS  Google Scholar 

  14. Dickeson, S.K., Bhattacharyya-Pakrasi, M., Mathis, N.L., Schlesinger, P.H. & Santoro, S.A. Biochemistry 37, 11280–11288 (1998).

    Article  CAS  Google Scholar 

  15. Huth, J.R. et al. Proc. Natl. Acad. Sci. U S A 97, 5231–5236 (2000).

    Article  CAS  Google Scholar 

  16. McDowall, A., Leitinger, B., Stanley, P., Bates, P.A., Randi, A. & Hogg, N. J. Biol. Chem. 273, 27396–27403 (1998).

    Article  Google Scholar 

  17. Zhang, L. & Plow, E.F. J. Biol. Chem. 271, 29953–29957 (1996).

    Article  CAS  Google Scholar 

  18. Kallen, J. et al. J. Mol. Biol. 292, 1–9 (1999).

    Article  CAS  Google Scholar 

  19. Oxvig, C., Lu, C. & Springer, T.A. Proc. Natl. Acad. Sci. USA 96, 2215–2220 (1999).

    Article  CAS  Google Scholar 

  20. Dahiyat, B.I. & Mayo, S.L. Science 278, 82–87 (1997).

    Article  CAS  Google Scholar 

  21. Irie, A., Kamata, T. & Takada, Y. Proc. Natl. Acad. Sci. USA 94, 7198–7203 (1997).

    Article  CAS  Google Scholar 

  22. Cierniewski, C.S. et al. J. Biol. Chem. 274, 16923–16932 (1999).

    Article  CAS  Google Scholar 

  23. Hantgan, R.R., Paumi, C., Rocco, M. & Weisel, J.W. Biochemistry 38, 14461–14474 (1999).

    Article  CAS  Google Scholar 

  24. Stephens, P.E., Ortlepp, S., Perkins, V.C., Robinson, M.K. & Kirby, H. Cell Adhes. Commun. 7, 377–390 (2000).

    Article  CAS  Google Scholar 

  25. Pampori, N. et al., J. Biol. Chem. 274, 21609–21616 (1999).

    Article  CAS  Google Scholar 

  26. Puzon-McLaughlin, W., Kamata, T. & Takada, Y. J. Biol. Chem. 275, 7795–7802 (2000).

    Article  CAS  Google Scholar 

  27. Zang, Q., Lu, C., Huang, C., Takagi, J. & Springer, T.A. J. Biol. Chem., in press (2000).

  28. Hughes, P.E. et al. J. Biol. Chem. 271, 6571–6574 (1996).

    Article  CAS  Google Scholar 

  29. Vinogradova, O., Haas, T., Plow, E.F. & Qin, J. Proc. Natl. Acad. Sci. U S A 97, 1450–1455 (2000).

    Article  CAS  Google Scholar 

  30. Bork, P., Doerks, T., Springer, T.A. & Snel, B. Trends Biochem. Sci. 24, 261–263 (1999).

    Article  CAS  Google Scholar 

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Correspondence to Birgit Leitinger or Nancy Hogg.

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Leitinger, B., Hogg, N. From crystal clear ligand binding to designer I domains. Nat Struct Mol Biol 7, 614–616 (2000). https://doi.org/10.1038/77895

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