Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
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Strategy for Determining the Structures of Large Biomolecules using the Torsion Angle Dynamics of CYANA

  • Jee, Jun-Goo (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University)
  • Received : 2016.11.15
  • Accepted : 2016.12.02
  • Published : 2016.12.20
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Abstract

With the rapid increase of data on protein-protein interactions, the need for delineating the 3D structures of huge protein complexes has increased. The protocols for determining nuclear magnetic resonance (NMR) structure can be applied to modeling complex structures coupled with sparse experimental restraints. In this report, I suggest the use of multiple rigid bodies for improving the efficiency of NMR-assisted structure modeling of huge complexes using CYANA. By preparing a region of known structure as a new type of residue that has no torsion angle, one can facilitate the search of the conformational spaces. This method has a distinct advantage over the rigidification of a region with synthetic distance restraints, particularly for the calculation of huge molecules. I have demonstrated the idea with calculations of decaubiquitins that are linked via Lys6, Lys11, Lys27, Lys29, Lys33, Lys48, or Lys63, or head to tail. Here, the ubiquitin region consisting of residues 1-70 was treated as a rigid body with a new residue. The efficiency of the calculation was further demonstrated in Lys48-linked decaubiquitin with ambiguous distance restraints. The approach can be readily extended to either protein-protein complexes or large proteins consisting of several domains.

Keywords

Acknowledgement

Supported by : National Research Foundation

References

  1. K. Wuthrich, NMR of Proteins and Nucleic Acids; Wiley: New York (1986)
  2. T. Herrmann, P. Guntert, and K. Wuthrich, J. Mol. Biol. 319, 209 (2002) https://doi.org/10.1016/S0022-2836(02)00241-3
  3. J. G. Jee, and P. Guntert, J. Struct. Funct. Genomics 4, 179 (2003) https://doi.org/10.1023/A:1026122726574
  4. C. Dominguez, R. Boelens, and A. M. Bonvin, J. Am. Chem. Soc. 125, 1731 (2003) https://doi.org/10.1021/ja026939x
  5. T. A. Hopf, C. P. Scharfe, J. P. Rodrigues, A. G. Green, O. Kohlbacher, C. Sander, A. M. Bonvin, and D. S. Marks, Elife 3:e03430 (2014)
  6. P. Guntert, C. Mumenthaler, and K. Wuthrich, J. Mol. Biol. 273, 283 (1997) https://doi.org/10.1006/jmbi.1997.1284
  7. M. P. Williamson, and C. J. Craven, J. Biomol. NMR 43, 131 (2009) https://doi.org/10.1007/s10858-008-9295-6
  8. D. Komander, and M. Rape, Annu. Rev. Biochem. 81, 203 (2012) https://doi.org/10.1146/annurev-biochem-060310-170328
  9. E. J. Eddins, R. Varadan, D. Fushman, C. M. Pickart, and C. Wolberger, J. Mol. Biol. 367, 204 (2007) https://doi.org/10.1016/j.jmb.2006.12.065
  10. T. Tenno, K. Fujiwara, H. Tochio, K. Iwai, E. H. Morita, H. Hayashi, S. Murata, H. Hiroaki, M. Sato, K. Tanaka, and M. Shirakawa, Genes Cells 9, 865 (2004) https://doi.org/10.1111/j.1365-2443.2004.00780.x
  11. R. Varadan, O. Walker, C. Pickart, and D. Fushman, J. Mol. Biol. 324, 637 (2002) https://doi.org/10.1016/S0022-2836(02)01198-1
  12. W. J. Cook, L.C. Jeffrey, E. Kasperek, and C. M. Pickart, J. Mol. Biol. 236, 601 (1994) https://doi.org/10.1006/jmbi.1994.1169
  13. J. G. Jee, Bull. Korean Chem. Soc. 35, 1944 (2014) https://doi.org/10.5012/bkcs.2014.35.7.1944
  14. J. G. Jee, J. Kor. Magn. Reson. Soc. 18, 24 (2014) https://doi.org/10.6564/JKMRS.2014.18.1.024
  15. J. G. Jee, J. Kor. Magn. Reson. Soc. 17, 11 (2013) https://doi.org/10.6564/JKMRS.2013.17.1.011
  16. A. W. Gotz, M. J. Williamson, D. Xu, D. Poole, S. Le Grand, and R. C. Walker, J. Chem. Theory. Comput. 8, 1542 (2012) https://doi.org/10.1021/ct200909j
  17. R. Salomon-Ferrer, A.W. Gotz, D. Poole, S. Le Grand, and R.C. Walker, J. Chem. Theory. Comput. 9, 3878 (2013) https://doi.org/10.1021/ct400314y
  18. J. G. Jee, J. Kor. Magn. Reson. Soc. 18, 69 (2014) https://doi.org/10.6564/JKMRS.2014.18.2.069