Journal of Protein Chemistry

, Volume 15, Issue 2, pp 161–168 | Cite as

Knowledge-based model building of the tertiary structures for lectin domains of the selectin family

  • Kuo-Chen Chou


A combination of a knowledge-based approach and energy minimization was used to predict the three-dimensional structures of the lectin domains of P-selectin, E-selectin, and L-selectin, respectively. Each of these domains contains 118 amino acids. The starting points for energy minimization were generated based on a framework that consists of a number of separated segments derived from the structure-known carbohydrate-recognition domain of the mannose-binding protein (MBP), which belongs to the same C-type lectin family as the selectin molecules do. The structures thus found for P-, L-, and E-selectin lectin domains share a common feature, i.e., they all contain twoα-helices, and two antiparallelΒ-sheets of which one is formed by two strands (strands 1 and 5) and the other by three (strands 2, 3, and 4). Besides, they all possess two intact disulfide bonds formed by the pair of Cys-19 and Cys-117, and the pair of Cys-90 and Cys-109. The root-meansquare deviations calculated over the set of backbone atoms between P- and L-selectin lectin domains is 3.10 å, that between P- and E-selectin lectin domains 2.48 å, and that between L- and E-selectin lectin domains 3.07 å. A notable feature is the convergencedivergence duality of the 77–107 polypeptide in the three domains; i.e., part of the peptide is folded into a closely similar conformation, and part of it into a highly different one.

Key words

P-selectin E-selectin L-selectin convergence-divergence duality energy minimization ECEPP 


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  1. Bevilacqua, M. P. A. (1993). Endothelial-leukocyte adhesion molecules,Annu. Rev. Immunol. 11, 767–804.PubMedGoogle Scholar
  2. Bevilacqua, M. P. A., Pober, J. S., Mendrick, D. L., Cotran, R. S., and Gimbrone, M. A., Jr. (1987). Identification of an inducible endothelial-leukocyte adhesion molecule,Proc. Natl. Acad. Sci. USA 84, 9238–9242.PubMedGoogle Scholar
  3. Bevilacqua, M. P., Stenglin, S., Gimbrone, M. A., Jr., and Seed, B. (1989). Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins,Science 243, 1160–1165.PubMedGoogle Scholar
  4. Bonfanti, R., Furie, B., and Wagner, D. (1989). PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cellsBlood 73, 1109–1112.PubMedGoogle Scholar
  5. Butcher, E. C. (1991). Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity,Cell 67, 1033–1036.PubMedGoogle Scholar
  6. Camerini, D., James, S. P., Stamenkovic, I., and Seed, B. (1989). Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor,Nature 342, 78–82.PubMedGoogle Scholar
  7. Carlacci, L., Chou, K. C., and G. M. Maggiora (1991). A heuristic approach to predicting the tertiary structure of bovine somatotropin,Biochemistry 30, 4389–4398.PubMedGoogle Scholar
  8. Chou, K. C. (1992). Energy-optimized structure of antifreeze protein and its binding mechanism,J. Mol. Biol. 223, 509–517.PubMedGoogle Scholar
  9. Chou, K. C. (1995). The convergence-divergence duality in lectin domains of selectin family and its implications,FEBS Lett. 363, 123–126.PubMedGoogle Scholar
  10. Chou, K. C., and Carlacci, L. (1991). Energetic approach to the folding ofα/Β barrels,Proteins Struct. Funct. Genet. 9, 280–295.PubMedGoogle Scholar
  11. Chou, K. C. and Scheraga, H. A. (1982). Origin of the right-handed twist ofΒ-sheets of poly(l-Val) chains,Proc. Natl. Acad. Sci. USA 79, 7047–7051.PubMedGoogle Scholar
  12. Chou, K. C., Némethy, G., and Scheraga, H. A. (1984). Energy approach to the packing ofα-helices,J. Am. Chem. Soc. 106, 3161–3170.Google Scholar
  13. Chou, K. C., Némethy, G., Pottle, M., and Scheraga, H. A. (1989). Energy of stabilization of the right-handedΒαΒ crossover in proteins,J. Mol. Biol. 205, 241–249.PubMedGoogle Scholar
  14. Drickamer, K. (1988). Two distinct classes of carbohydrate-recognition domains in animal lectins,J. Biol. Chem. 263, 9557–9560.PubMedGoogle Scholar
  15. Drickamer, K., Dordal, M. S., and Reynolds, L. (1986). Mannose-binding proteins isolated from rat liver contain carbohydrate-recognition domains linked to collagenous tails—Complete primary structures and homology with pulmonary surfactant apoprotein,J. Biol. Chem. 261, 6878–6887.PubMedGoogle Scholar
  16. Erbe, D. V., Wolitzky, B. A., Presta, L. G., Norton, C. R., Ramos, R. J., Burns, D. K., Rumberger, J. M., Rao, B. N. N., Foxall, C., Brandly, B. K., and Lasky, L. A. (1992). Identification of an E-selectin region critical for carbohydrate recognition and cell adhesion,J. Cell. Biol. 119, 215–227.PubMedGoogle Scholar
  17. Gellatin, M., St. John, T. P., Siegelman, M., Reichert, R., Butcher, E. C., and Weissman, I. L. (1986). Lymphocyte homing reseptors,Cell 44, 673–680.PubMedGoogle Scholar
  18. Gay, D. M. (1983). Subroutines for unconstrained minimization using a model/trust-region approach,Assoc. Comput. Mach. Trans. Math. Software 9, 503–524.Google Scholar
  19. Graves, B. J., Crowther, R. L., Chandran, C., Rumberger, J. M., Li, S., Huang, K. S., Presky, D. H., Familletti, P. C., Wolitzky, B. A., and Burns, D. K. (1994). Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains.Nature 367, 532–538.PubMedGoogle Scholar
  20. Hollenbaugh, D., Bajorath, J., Stenkamp, R., and Aruffo, A. (1993). Interaction of P-selectin (CD62) and its cellular ligand: Analysis of critical residues,Biochemistry 32, 2960–2966.PubMedGoogle Scholar
  21. IUPAC-IUB Commission on Biochemical Nomenclature (1970). Abbreviations and symbols for the description of the conformation of polypeptide chains,Biochemistry 9, 3471–3479.Google Scholar
  22. Johnston, G. I., Cook, R. G., and McEver, R. P. (1989). Cloning of GMP-140, a granule membrane protein of platelets and endothelium: Sequence similarity to proteins involved in cell adhesion and inflammation,Cell 56, 1033–1044.PubMedGoogle Scholar
  23. Lasky, L. A. (1992). Selectins: Interpreters of cell-specific carbohydrate information during inflammation,Science 258, 964–969.PubMedGoogle Scholar
  24. Lasky, L. A., Singer, M. S., Yednock, T. A., Dowbenko, D., Fennie, C., Rodriguez, H., Nguyen, T., Stachel, S., and Rosent, S. D. (1989). Cloning of a lymphocyte homing receptor reveals a lectin domain,Cell 56, 1045–1055.PubMedGoogle Scholar
  25. Lasky, L. A., Singer, M. S., Dowbenko, D., Imai, Y. Henzel, W. J., Grimley, C., Fennie, C., Gillett, N., Watson, S. R., and Rosent, S. D. (1992). An endothelial ligand for L-selectin is a novel mucin-like molecule,Cell 69, 927–938.PubMedGoogle Scholar
  26. Mills, A. (1993). Modelling the carbohydrate recognition domain of human E-selectin,FEBS Lett. 319, 5–11.PubMedGoogle Scholar
  27. Momany, F. A., McGuire, R. F., Burgess, A. W., and Scheraga, H. A. (1975). Energy parameters in polypeptides. 7. Geometrical parameters, partial atomic charges, nonbonded interactions, hydrogen bond interactions, and intrinsic torsional potentials for the naturally occurring amino acids,J. Phys. Chem. 79, 2361–2381.Google Scholar
  28. Némethy, G., Pottle, M. S., and Scherage, H. A. (1983). Energy parameters in polypeptides. 9. Updating of geometrical parameters, nonbonded interactions, and hydrogen bond interactions for the naturally occurring amino acids,J. Phys. Chem. 87, 1883–1887.CrossRefGoogle Scholar
  29. Siegelman, M. H., and Weissman, I. L. (1989). Human homologue of mouse lymph node homing receptor: Evolutionary conservation at tandem cell interaction domains,Proc. Natl. Acad. Sci. USA 86, 5562–5566.PubMedGoogle Scholar
  30. Siegelman, M. H., van de Rijn, M., and Weissman, I. L. (1989). Mouse lymph node homing receptor cDNA clone encodes a glycoprotein revealing tandem interaction domains,Science 243, 1165–1172.PubMedGoogle Scholar
  31. Smith, R. F., and Smith, T. F. (1992). Pattern-induced multisequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling,Protein Eng. 5, 35–41.PubMedGoogle Scholar
  32. Vásquez, M., Némethy, G., and Scheraga, H. A. (1983). Computed conformational states of the 20 naturally occurring amino acid residues and of the prototype residueα-aminobutyric acid,Macromolecules 16, 1043–1049.Google Scholar
  33. Watson, S. R., Fennie, C., and Lasky, L. A. (1991). Neutrophil influx into an inflammatory site inhibited by a soluble homing receptor-IgG chimaera,Nature 349, 164–167.PubMedGoogle Scholar
  34. Weis, W. I., Kahn, R., Fourme, R., Drickamer, K., and Hendrickson, W. A. (1991). Structure of the calciumdependent lectin domain from a rat manose-binding protein determined by MAD phasing,Science 254, 1608–1615.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Kuo-Chen Chou
    • 1
  1. 1.Computer-Aided Drug Discovery, Upjohn LaboratoriesPharmacia & Upjohn Inc.Kalamazoo

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