Small-Angle Solution Scattering Reveals Information on Conformational Dynamics in Calcium-Binding Proteins and in their Interactions with Regulatory Targets
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Abstract
When a beam of neutrons or X-rays encounters a protein in solution, a small portion of the beam will be deflected or “scattered.” The angular dependence of this scattering is related to the structure of the protein. For a solution of randomly oriented proteins, the scattering is concentrated in the vicinity of the direct beam, or zero-angle. Solution scattering is therefore often referred to as small-angle or low-angle scattering. Structural information encoded in the scattering data includes the overall size and shape of the protein. Although this information is relatively low-resolution, it is not limited by the requirement of having crystals and it can be applied to structures with dimensions in the range 10-1000 Å. This range is extremely useful for studies of proteins and the complexes they form.
Keywords
Neutron Experiment Partial Specific Volume Phosphorylase Kinase Catalytic Cleft Hydrophobic CleftReferences
- 1.Glatter, O. and Kratky, O. (1982) Small Angle X-ray Scattering. Academic, London and New York.Google Scholar
- 2.Feigin, L. A. and Svergun, D. I. (1987) Structure Analysis by Small-Angle X-ray and Neutron Scattering. Plenum, New York and London.Google Scholar
- 3.Trewhella, J., Gallagher, S. C., Krueger, J. K., and Zhao, J. (1998) Neutron and x-ray solution scattering provide insights into biomolecular structure and function. Science Progress 81, 101–122.PubMedGoogle Scholar
- 4.Wu, C.-F. and Chen, S.-H. (1988) Small angle neutron and x-ray scattering studies of concentrated protein solutions II. Cytochrome c. Biopolymers 27, 1065–1083.PubMedCrossRefGoogle Scholar
- 5.Krigbaum, W. R. and Kugler, F. R. (1970) Molecular conformation of egg-white lysozyme and bovine (-lactalbumin in solution. Biochemistry 9, 1216–1223.PubMedCrossRefGoogle Scholar
- 6.Guinier, A. and Fournet, G. (1955) Small-Angle Scattering of X-rays. Wiley, New York.Google Scholar
- 7.Moore, P. B. (1980) Small angle scattering information content and error analysis. J. Appl. Cryst. 13, 168–175.CrossRefGoogle Scholar
- 8.Glatter, O. (1979) The interpretation of real-space information from small-angle scattering experiments. J. Appl. Cryst. 12, 166–175.CrossRefGoogle Scholar
- 9.Svergun, D. I., Semenyuk, A. V., and Feigen, L. A. (1988) Small-angle scattering data treatment by the regularization method. Acta Cryst. A44, 244–250.Google Scholar
- 10.Heidorn, D. B. and Trewhella, J. (1988) Comparison of the crystal and solution structures of calmodulin and troponin C. Biochemistry 27, 909–915.PubMedCrossRefGoogle Scholar
- 11.Krueger, J. K., Olah, G. A., Rokop, S. E., Zhi, G., Stull, J. T., and Trewhella, J. (1997) The structure of 4Ca2+·calmodulin and a functional myosin light chain kinase in the activated complex. Biochemistry 36, 6017–6023.PubMedCrossRefGoogle Scholar
- 12.Krueger, J., Zhi, G., Stull, J. T., and Trewhella, J. (1998) Neutron scattering studies reveal further details of the Ca2+/calmodulin-dependent activation mechanism of myosin light chain kinase. Biochemistry 37, 13,997–14,004.PubMedCrossRefGoogle Scholar
- 13.Knighton, D. R., Zheng, J. H., Ten Eyck, L. F., Ashford, V. A., Xuong, N. H., Taylor, S. S., and Sowadski J. M. (1991) Crystal structure of the catalytic subunit of cAMP-dependent protein kinase. Science 253, 407–414.PubMedCrossRefGoogle Scholar
- 14.Krueger, J. K., Padre, R. C., and Stull, J. T. (1995) Intrasteric regulation of myosin light chain kinase. J. Biol. Chem. 270, 16,848–16,853.PubMedCrossRefGoogle Scholar
- 15.Babu, Y. S., Sack, J. S., Greenhough, T. J., Bugg, C. E., Means, A. R., and Cook, W. J., (1985) Three-dimensional structure of calmodulin. Nature 315, 37–40.PubMedCrossRefGoogle Scholar
- 16.Ikura, M. (1996) Calcium binding and conformational response ion EF-hand proteins. Trends Biochem. Sci. 21, 14–17.PubMedGoogle Scholar
- 17.Seaton, B. A., Head, J. F., Engelman, D. M., and Richards, F. M. (1985) Calcium-induced increase in the radius of gyration and maximum dimension of calmodulin measured by small-angle scattering. Biochemistry 24, 6740–6743.PubMedCrossRefGoogle Scholar
- 18.Trewhella, J. (1992) The solution structures of calmodulin and its complexes with peptides based on target enayme binding domains. Cell Calcium 13, 407–420.CrossRefGoogle Scholar
- 19.Ikura, M., Clore, G. M., Gronenborn, A. M., Zhu, G., Klee, C. B., and Bax, A. (1992) Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256, 632–638.PubMedCrossRefGoogle Scholar
- 20.Persechini, A., Gansz, K. J., and Paresi, R. J. (1996) A role in enzyme activation for the N-terminal leader sequence in calmodulin. J. Biol. Chem. 271, 19,279–19,282.PubMedCrossRefGoogle Scholar
- 21.Krueger, J., Bishop, N. A., Blumenthal, D. K., Zhi, G., Beckingham, K., Stull, J. T., and Trewhella, J. (1998) Calmodulin binding to myosin light chain kinase begins at substoichiometric Ca2+concentrations: a small-angle scattering study of binding and of conformational transitions. Biochemistry 37, 17,810–17,817.PubMedCrossRefGoogle Scholar
- 22.Bayley, P., Findlay, W. A., and Martin, S.R. (1996) Target recognition by calmodulin: dissecting the kinetics and affinity of interaction using short peptide sequences. Protein Sci. 5, 1215–1228.PubMedCrossRefGoogle Scholar
- 23.Peerson, O. B., Madson, T. S., and Falke, J. J. (1997) Intermolecular tuning of calmodulin by target peptides and proteins: differential effects on Ca2+binding and implications for kinase activation. Protein Sci. 6, 794–807.CrossRefGoogle Scholar
- 24.Trewhella, J., Blumenthal, D. K., Rokop, S. E., and Seeger, P. A. (1990) Small-angle scattering studies show distinct conformations of calmodulin in its complexes with two peptides based on the regulatory domain of the catalytic subunit of phos-phorylase kinase. Biochemistry 29, 9316–9324.PubMedCrossRefGoogle Scholar
- 25.Olah, G. A., Rokop, S. E., Wang, C.-L. A., Blechner, and S. L., Trewhella, J. (1994) Troponin I encompasses an extended troponin C in the Ca2+bound complex: a small-angle x-ray and neutron scattering study. Biochemistry 33, 8233–8239.PubMedCrossRefGoogle Scholar
- 26.Stone, D. B., Timmins, P. A., Schneider, D. K., Krylova, I., Ramos, C. H. I., Reinach, F. C., and Mendelson, R. A. (1998) The effect of regulatory Ca2+on the in situ structures of troponin C and troponin I: a neutron scattering study. J. Mol. Biol. 281, 689–704.PubMedCrossRefGoogle Scholar
- 27.Olah, G. A. and Trewhella, J. (1994) A model structure of the muscle protein complex 4Ca2+·troponin C·troponin I derived from small-angle scattering data: implications for regulation. Biochemistry 33, 12,800–12,806.PubMedCrossRefGoogle Scholar
- 28.Tung, C.-S., Wall, M. E., Gallagher, S. C., and Frewella, J. (2000) A model of troponin-I in complex with troponin-C using hybrid experimental data: The inhibitory region is a B-hairpin. Protein Science 9, 1312–1326.PubMedCrossRefGoogle Scholar
- 29.Zaccai, G. and Jacrot, B. (1983) Small angle neutron scattering. Ann Rev. Biophys. Bioeng. 12, 139–157.+CrossRefGoogle Scholar