More precise model of α-helix and transmembrane α-helical peptide backbone structure
Affiliation(s)
Agricultural Research Service, USA Department of Agriculture, Beltsville, USA. Department of Engineering, Morgan State University, Baltimore, USA.
Agricultural Research Service, USA Department of Agriculture, Beltsville, USA. Department of Engineering, Morgan State University, Baltimore, USA.
ABSTRACT
The 3-D structure of the β-adrenergic receptor with a molecular weight of 55,000 daltons is available from crystallographic data. Within one of the seven transmembrane ion channel helices in the β2-receptor, one loop of a helix ACADL has previously been proposed as the site that explains β2 activity (fights acute bronchitis) whereas ASADL in the β1-receptor at the corresponding site explains β1-activity (cardiac stimulation). The α-agonist responsible for this selective reaction is only 0.5% of the receptor molecular weight, and only 1.5% of the weight of the trans-membrane portion of the receptor. The understanding of the mechanism by which a small molecule on binding to a site on one single loop of a helix produces a specific agonist activity on an entire transmembrane ion channel is uncertain. A model of an α-helix is presented in which of pitch occurs at angles both smaller and larger than 180° n. Consequently, atomic coordinates in a peptide backbone α-helix match the data points of individual atom (and atom types) in the backbone. More precisely, eleven atoms in peptide backbone routinely equal one loop of a helix, instead of eleven amino acid residues equaling three loops of a helix; therefore, an α-helix can begin (or end) at any specific atom in a peptide backbone, not just at any specific amino acid. Wavefront Topology System and Finite Element Methods calculate this specific helical shape based only upon circumference, pitch, and phase. Only external forces which specifically affect circumference, pitch and/or phase (e.g. from agonist binding) can/will alter the shape of an α-helix.
The 3-D structure of the β-adrenergic receptor with a molecular weight of 55,000 daltons is available from crystallographic data. Within one of the seven transmembrane ion channel helices in the β2-receptor, one loop of a helix ACADL has previously been proposed as the site that explains β2 activity (fights acute bronchitis) whereas ASADL in the β1-receptor at the corresponding site explains β1-activity (cardiac stimulation). The α-agonist responsible for this selective reaction is only 0.5% of the receptor molecular weight, and only 1.5% of the weight of the trans-membrane portion of the receptor. The understanding of the mechanism by which a small molecule on binding to a site on one single loop of a helix produces a specific agonist activity on an entire transmembrane ion channel is uncertain. A model of an α-helix is presented in which of pitch occurs at angles both smaller and larger than 180° n. Consequently, atomic coordinates in a peptide backbone α-helix match the data points of individual atom (and atom types) in the backbone. More precisely, eleven atoms in peptide backbone routinely equal one loop of a helix, instead of eleven amino acid residues equaling three loops of a helix; therefore, an α-helix can begin (or end) at any specific atom in a peptide backbone, not just at any specific amino acid. Wavefront Topology System and Finite Element Methods calculate this specific helical shape based only upon circumference, pitch, and phase. Only external forces which specifically affect circumference, pitch and/or phase (e.g. from agonist binding) can/will alter the shape of an α-helix.
KEYWORDS
Helix; Alpha-Helix; Circumference; Pitch, phase; peptide backbone; Wavefront Topology System; Finite Element Method
Helix; Alpha-Helix; Circumference; Pitch, phase; peptide backbone; Wavefront Topology System; Finite Element Method
Cite this paper
F. Schmidt, W. and G. Thomas, C. (2012) More precise model of α-helix and transmembrane α-helical peptide backbone structure. Journal of Biophysical Chemistry, 3, 295-303. doi: 10.4236/jbpc.2012.34036.
F. Schmidt, W. and G. Thomas, C. (2012) More precise model of α-helix and transmembrane α-helical peptide backbone structure. Journal of Biophysical Chemistry, 3, 295-303. doi: 10.4236/jbpc.2012.34036.
References
[1] Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K. and Stevens, R.C. (2007) High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science, 318, 1258-1265. doi:10.1126/science.1150577 [2] Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C. and Kobilka, B.K. (2007) GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science, 318, 1266-1273. doi:10.1126/science.1150609 [3] Rasmussen, S.G., Choi, H.J., Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Ratnala, V.R., Sanishvili, R., Fischetti, R.F., Schertler, G.F., Weis, W.I. and Kobilka, B.K. (2007) Crystal structure of the human β2-adrenergic G-protein-coupled receptor. Nature, 450, 383-387. doi:10.1038/nature06325 [4] Becker, L.A., Hom, J., Villasis-Keever, M. and van der Wouden, J.C. (2011) Beta2-agonists for acute bronchitis. Cochrane Database Systematic Reviews, 7, CD001726. [5] Strader, C.D., Sigal, I.S. and Dixon, R.A.F. (1989) Structural basis of beta-adrenergic receptor function. FASEB Journal, 3, 1825-1832. [6] Schmidt, W., Honigberg, I. L., Van Halbeek, H., Waters, R. M. and Mitchell, A.D. (1993) Association of β-Agonists with corresponding β2-and β1-adrenergic pentapeptide sequences. International Journal of Peptide Protein Research, 41, 467-475. doi:10.1111/j.1399-3011.1993.tb00466.x [7] Kontoyianni, M., DeWeese, C., Penzotti, J. E. and Lybrand T.P. (1996) Three-dimensional models for agonist and antagonist complexes with β2 adrenergic receptor. Journal of Medicinal Chemistry, 39, 4406-4420. doi:10.1021/jm960241a [8] Schmidt, W.F. and Gassner, G. (1995) Chirality and computational chemistry: A new direction. Current Medicinal Chemistry, 1, 502-510. [9] Jordan, P.C., Bacquet, R.J., McCammon, J.A. and Tran, P. (1989) How electrolyte shielding influences electrical potential in transmembrane channels. Biophysical Journal, 55, 1041-1052. doi:10.1016/S0006-3495(89)82903-0 [10] Yeagle, P.L., Bennett, M., Lemaitre, V. and Watts, A. (2007) Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch. Biochimica et Biophysica Acta (BBA)—Biomembranes, 1768, 530-537. doi:10.1016/j.bbamem.2006.11.018 [11] Sheridan, R.P. and Allen, L.C. (1980) The electrostatic potential of the alpha helix (electrostatic potential/α-helix/secondary structure/helix dipole). Biophysical Chemistry, 11, 133-136. doi:10.1016/0301-4622(80)80015-9 [12] Hol, W.G. (1985) Effects of the alpha-helix dipole upon the functioning and structure of proteins. Advances in Biophysics, 19, 133-165. doi:10.1016/0065-227X(85)90053-X [13] Sadiko, M.N.O. (1992) Numerical Techniques in Electro- magnetism, CRC Press LLC, Boco Raton. [14] Chatterjee, A., Jin, J.M., and Volakis, J.L. (1993) Edge- based finite elements and vector ABSs applied to 3-D scattering. IEEE Transactions on Antennas and Propagation, 41, 221-226. [15] Xingchao, Y. (1990) Three-dimensional elecromagnetic scattering from inhomogeneous objects by hybrid moment and finite element method. IEEE Transactions on Microwave Theory and Techniques, 38, 1053-1058. [16] Thomas, C.G. (2012) Wavefront topology system and finite element method applied to engineering visualization. Ph.D. Dissertation, Morgan State University, Baltimore. [17] Castellan, G.W. (1983) Physical chemistry. Addison-Wesley Publishing Company, Reading, 580. [18] Imai, H., Hirano, T., Kandori, H., Terakita, A. and Shichida Y. (2001) Difference in molecular structure of rod and cone visual pigments studied by fourier transform infrared spectroscopy. Biochemistry, 40, 2879-2886. doi:10.1021/bi002227c [19] Schmidt, W. F. and Jayasundera, S. (2003) Microcrystal- line Keratin Fiber. In: Wallenberger, F. and Weston, N. Eds., Natural Fibers Plastics and Composites—Recent Advances, Kluwer Academic Publishers, Norwell, 51-66. [20] Elsasser, T.H., Li, C.-J., Caperna, T.J., Kahl, S. and Schmidt, W.F. (2007) Growth hormone (GH) associated nitration of janus kinase-2 at the 1007Y-1008Y epitope impedes phosphorylation at this site: Mechanism for and impact of a GH, AKT, and nitric oxide synthase axis on GH signal transduction. Endocrinology, 148, 3792-3802. doi:10.1210/en.2006-1736
[1] Cherezov, V., Rosenbaum, D.M., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Kuhn, P., Weis, W.I., Kobilka, B.K. and Stevens, R.C. (2007) High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor. Science, 318, 1258-1265. doi:10.1126/science.1150577 [2] Rosenbaum, D.M., Cherezov, V., Hanson, M.A., Rasmussen, S.G., Thian, F.S., Kobilka, T.S., Choi, H.J., Yao, X.J., Weis, W.I., Stevens, R.C. and Kobilka, B.K. (2007) GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science, 318, 1266-1273. doi:10.1126/science.1150609 [3] Rasmussen, S.G., Choi, H.J., Rosenbaum, D.M., Kobilka, T.S., Thian, F.S., Edwards, P.C., Burghammer, M., Ratnala, V.R., Sanishvili, R., Fischetti, R.F., Schertler, G.F., Weis, W.I. and Kobilka, B.K. (2007) Crystal structure of the human β2-adrenergic G-protein-coupled receptor. Nature, 450, 383-387. doi:10.1038/nature06325 [4] Becker, L.A., Hom, J., Villasis-Keever, M. and van der Wouden, J.C. (2011) Beta2-agonists for acute bronchitis. Cochrane Database Systematic Reviews, 7, CD001726. [5] Strader, C.D., Sigal, I.S. and Dixon, R.A.F. (1989) Structural basis of beta-adrenergic receptor function. FASEB Journal, 3, 1825-1832. [6] Schmidt, W., Honigberg, I. L., Van Halbeek, H., Waters, R. M. and Mitchell, A.D. (1993) Association of β-Agonists with corresponding β2-and β1-adrenergic pentapeptide sequences. International Journal of Peptide Protein Research, 41, 467-475. doi:10.1111/j.1399-3011.1993.tb00466.x [7] Kontoyianni, M., DeWeese, C., Penzotti, J. E. and Lybrand T.P. (1996) Three-dimensional models for agonist and antagonist complexes with β2 adrenergic receptor. Journal of Medicinal Chemistry, 39, 4406-4420. doi:10.1021/jm960241a [8] Schmidt, W.F. and Gassner, G. (1995) Chirality and computational chemistry: A new direction. Current Medicinal Chemistry, 1, 502-510. [9] Jordan, P.C., Bacquet, R.J., McCammon, J.A. and Tran, P. (1989) How electrolyte shielding influences electrical potential in transmembrane channels. Biophysical Journal, 55, 1041-1052. doi:10.1016/S0006-3495(89)82903-0 [10] Yeagle, P.L., Bennett, M., Lemaitre, V. and Watts, A. (2007) Transmembrane helices of membrane proteins may flex to satisfy hydrophobic mismatch. Biochimica et Biophysica Acta (BBA)—Biomembranes, 1768, 530-537. doi:10.1016/j.bbamem.2006.11.018 [11] Sheridan, R.P. and Allen, L.C. (1980) The electrostatic potential of the alpha helix (electrostatic potential/α-helix/secondary structure/helix dipole). Biophysical Chemistry, 11, 133-136. doi:10.1016/0301-4622(80)80015-9 [12] Hol, W.G. (1985) Effects of the alpha-helix dipole upon the functioning and structure of proteins. Advances in Biophysics, 19, 133-165. doi:10.1016/0065-227X(85)90053-X [13] Sadiko, M.N.O. (1992) Numerical Techniques in Electro- magnetism, CRC Press LLC, Boco Raton. [14] Chatterjee, A., Jin, J.M., and Volakis, J.L. (1993) Edge- based finite elements and vector ABSs applied to 3-D scattering. IEEE Transactions on Antennas and Propagation, 41, 221-226. [15] Xingchao, Y. (1990) Three-dimensional elecromagnetic scattering from inhomogeneous objects by hybrid moment and finite element method. IEEE Transactions on Microwave Theory and Techniques, 38, 1053-1058. [16] Thomas, C.G. (2012) Wavefront topology system and finite element method applied to engineering visualization. Ph.D. Dissertation, Morgan State University, Baltimore. [17] Castellan, G.W. (1983) Physical chemistry. Addison-Wesley Publishing Company, Reading, 580. [18] Imai, H., Hirano, T., Kandori, H., Terakita, A. and Shichida Y. (2001) Difference in molecular structure of rod and cone visual pigments studied by fourier transform infrared spectroscopy. Biochemistry, 40, 2879-2886. doi:10.1021/bi002227c [19] Schmidt, W. F. and Jayasundera, S. (2003) Microcrystal- line Keratin Fiber. In: Wallenberger, F. and Weston, N. Eds., Natural Fibers Plastics and Composites—Recent Advances, Kluwer Academic Publishers, Norwell, 51-66. [20] Elsasser, T.H., Li, C.-J., Caperna, T.J., Kahl, S. and Schmidt, W.F. (2007) Growth hormone (GH) associated nitration of janus kinase-2 at the 1007Y-1008Y epitope impedes phosphorylation at this site: Mechanism for and impact of a GH, AKT, and nitric oxide synthase axis on GH signal transduction. Endocrinology, 148, 3792-3802. doi:10.1210/en.2006-1736