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2001 | 48 | 1 | 53-64
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Novel approach to computer modeling of seven-helical transmembrane proteins: Current progress in the test case of bacteriorhodopsin.

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G-protein coupled receptors (GPCRs) are thought to be proteins with 7-membered transmembrane helical bundles (7TM proteins). Recently, the X-ray structures have been solved for two such proteins, namely for bacteriorhodopsin (BR) and rhodopsin (Rh), the latter being a GPCR. Despite similarities, the structures are different enough to suggest that 3D models for different GPCRs cannot be obtained directly employing 3D structures of BR or Rh as a unique template. The approach to computer modeling of 7TM proteins developed in this work was capable of reproducing the experimental X-ray structure of BR with great accuracy. A combination of helical packing and low-energy conformers for loops most close to the X-ray structure possesses the r.m.s.d. value of 3.13 Å. Such a level of accuracy for the 3D-structure prediction for a 216-residue protein has not been achieved, so far, by any available ab initio procedure of protein folding. The approach may produce also other energetically consistent combinations of helical bundles and loop conformers, creating a variety of possible templates for 3D structures of 7TM proteins, including GPCRs. These templates may provide experimentalists with various plausible options for 3D structure of a given GPCR; in our view, only experiments will determine the final choice of the most reasonable 3D template.
Physical description
  • 1. Marshall, G.R. (1997) Therapeutic approaches to human immunodeficiency virus structural studies on G-protein-coupled receptors. Pharmacol. Ther. 76, 135-139.
  • 2. Pebay-Peyroula, E., Rummel, G., Rosenbush, J.P. & Landau, E.M. (1997) X-Ray structure of bacteriorhodopsin at 2.5 ångstroms from microcrystals grown in lipidic cubic phases. Science 277, 1676-1681.
  • 3. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Trong, I.L., Teller, D.C., Okada, T., Stenkamp, R.E., Yamamoto, M. & Miyano, M. (2000) Crystal structure of rhodopsin, A G protein-coupled receptor. Science 289, 739- 745.
  • 4. Soppa, J. (1994) Two hypotheses one answer. Sequence comparison does not support an evolutionary link between halobacterial retinal proteins including bacteriorhodopsin and eukaryotic G-protein-coupled receptors. FEBS Lett. 342, 7-11.
  • 5. Kwong, P.D., Wyatt, R., Robinson, J., Sweet, R.W., Sodroski, R. & Hendrickson, W.A. (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659.
  • 6. Chollet, A. & Turcatti, G. (1999) Biophysical approaches to G protein-coupled receptors, Structure, function and dynamics. J. Comput. Aided Mol. Des. 13, 209-219.
  • 7. Alkorta, I. & Loew, G.H. (1996) A 3D model of the delta opioid receptor and ligand-receptor complexes. Protein Eng. 9, 573-583.
  • 8. Nemethy, G., Pottle, M.S. & Scheraga, H.A. (1983) Energy parameters in polypeptides. 9. Updating of geometrical parameters, nonbonded interactions, and hydrogen bond interactions for the naturally occuring amino acids. J. Phys. Chem. 87, 1883-1887.
  • 9. Dunfield, L.G., Burgess, A.W. & Scheraga, H.A. (1978) Energy parameters in polypeptides. 8. Empirical potential energy algorithm for the conformational analysis of large molecules. J. Phys. Chem. 82, 2609-2616.
  • 10. Nikiforovich, G.V. (1998) A novel, non-statistical method for predicting breaks in transmembrane helices. Protein Eng. 11, 279-283.
  • 11. Efimov, A.V. (1986) Standard conformations of a polypeptide chain in irregular protein regions. Molek. Biol. 20, 250-260 (in Russian).
  • 12. Efimov, A.V. (1991) Structure of α-α hairpins with short connections. Protein Eng. 4, 245-250.
  • 13. Deisenhofer, J., Epp, O., Sinning, I. & Michel, H. (1995) Crystallographic refinement at 2.3 Å resolution and refined model of the photosynthetic reaction centre from Rhodopseudomonas viridis. J. Mol. Biol. 246, 429-457.
  • 14. Iwata, S., Ostermeier, C., Ludwig, B. & Michel, H. (1995) Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376, 660-669.
  • 15. Rost, B., Casadio, R., Fariselli, P. & Sander, C. (1995) Transmembrane helices predicted at 95% accuracy. Protein Sci. 4, 521-533.
  • 16. Hirokawa, T., Boon-Chieng, S. & Mitaku, S. (1998) SOSUI: Classification and secondary structure prediction system for membrane proteins. Bioinformatics 14, 378-379.
  • 17. Cserzö, M., Bernassau, J.-M., Simon, I. & Maigret, B. (1994) New alignment strategy for transmembrane proteins. J. Mol. Biol. 243, 388-396.
  • 18. Gromiha, M.M. (1999) A simple method for predicting transmembrane α-helices with better accuracy. Protein Eng. 12, 557-561.
  • 19. Bowie, J.U. (1997) Helix packing in membrane proteins. J. Mol. Biol. 272, 780-789.
  • 20. Tseitin, V.M. & Nikiforovich, G.V. (1999) Isolated transmembrane helices arranged across a membrane, computational studies. Protein Eng. 12, 305-311.
  • 21. Hopfinger, A.J. (1973) Conformational Properties of Macromolecules. Academic Press, N.Y.
  • 22. Röper, D., Jacoby, E., Krüger, P., Engels, M., Grötzinger, J., Wollmer, A. & Strassburger, W. (1994) Modeling of G-protein coupled receptor with bacteriorhodopsin as a template. A novel approach based on interaction energy differences. J. Recept Res. 14, 167-186.
  • 23. Pogozheva, I.D., Lomize, A.L. & Mosberg, H.I. (1997) The transmembrane α-bundle of rhodopsin: Distance geometry calculations with hydrogen bonding constraints. Biophys. J. 72, 1963-1985.
  • 24. Schertler, G.F.X., Villa, C. & Henderson, R. (1993) Projection structure of rhodopsin. Nature 362, 770-772.
  • 25. Baldwin, J.M. (1993) The probable arrangement of the helices in G-protein-coupled receptors. EMBO J. 12, 1693-1703.
  • 26. Zhang, H., Lai, L., Wang, L., Han, Y. & Tang, Y. (1997) A fast and efficient program for modeling protein loops. Biopolymers 41, 61-72.
  • 27. van Vlijmen, H.W.T. & Karplus, M. (1997) PDB-based protein loop prediction: Parameters for selection and methods for optimization. J. Mol. Biol. 267, 975-1001.
  • 28. Carlacci, L. & Englander, S.W. (1993) The loop problem in proteins: A Monte Carlo simulated annealing approach. Biopolymers 33, 1271-1286.
  • 29. Bates, P.A. & Sternberg, M.J.E. (1999) Model building by comparison at CASP3: Using expert knowledge and computer automation. Proteins (Suppl.) 3, 47-54.
  • 30. Orengo, C.A., Bray, J.E., Hubbard, T., LoConte, L. & Sillitoe, I. (1999) Analysis and assessment of ab initio three-dimensional prediction, secondary structure, and contacts prediction. Proteins (Suppl.) 3, 149-170.
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