Abstract
Cryo-EM has become an increasingly powerful technique for elucidating the structure, dynamics and function of large flexible macromolecule assemblies that cannot be determined at atomic-resolution. A major challenge in analyzing EM maps of complexes is the identification of their subunits. We propose a fully automated highly efficient method for discovering high-resolution subunits of a complex, given as an intermediate resolution map, without prior knowledge of their boundaries and content. The method extracts helices from an EM map and uses their spatial arrangement to detect candidate subunits. The method was tested successfully on several simulated 8.0Å resolution maps. The obtained spatial helix arrangement was sufficient for the discovery of the correct subunits from a dataset of 887 SCOP representatives.
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References
Dutta, S., Berman, H.M.: Large macromolecular complexes in the protein data bank: A status report. Structure 13, 381–388 (2005)
Chiu, W., Baker, M.L., Jiang, W., Dougherty, M., Schmid, M.F.: Electron cryomicroscopy of biological machines at subnanometer resolution. Structure 13, 363–372 (2005)
Baumeister, W., Steven, A.: Macromolecular electron microscopy in the era of structural genomics. Trends. Biochem. Sci. 25, 624–631 (2000)
Harauz, G., Van Heel, M.: Exact filters for general geometry three dimensional recontruction. Proceedings of the IEEE Computer Vision and Pattern Recognition Conf. 73, 146–156 (1986)
Auer, M.: Three-dimentional electron cryo-microscopy as a powerful structural tool in molecular medicine. J. Mol. Med. 78, 191–202 (2000)
Rossmann, M.G., Morais, M.C., Leiman, P.G., Zhang, W.: Combining x-ray crystallography and electron microscopy. Structure 13, 355–362 (2005)
Jones, T., Zou, J., Cowan, S., Kjeldgaard, M.: Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A47, 110–119 (1991)
Humphrey, W., Dalke, A., Schulten, K.: VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996)
Volkmann, N., Hanein, D.: Docking of atomic models into reconstruction from electron microscopy. Methods Enzymol 374, 204–225 (2003)
Chacon, P., Wriggers, W.: Multiresolution contour-based fitting of macromolecular structure. J. Mol. Biol. 317, 375–384 (2002)
Jiang, W., Baker, M.L., Ludtke, S.J., Chiu, W.: Bridging the information gap: Computational tools for intermediate resolution structure interpretation. J. Mol. Biol. 208, 1033–1044 (2001)
Rossmann, M.G.: Fitting atomic models into electron-microscopy maps. Acta Crystallogr D56, 1341–1349 (2000)
Kleywegt, G.J., Jones, T.: Detecting folding motifs and similarities in protein structures. Methods Enzymol 277, 525–545 (1997)
Mizuguchi, K., Go, N.: Comparison of spatial arrangements of secondary structural elements in proteins. Protein Eng. 8, 353–362 (1995)
Gonzalez, R.C., Woods, R.E.: Digital Image Processing, second edition. Prentice Hall, Upper Saddle River (2002)
Ludtke, S.J., Baldwin, P.R., Chiu, W.: EMAN: Semiautomated software for high-resolution single-particle reconstructions. J. Struct. Biol. 128, 82–97 (1999)
Wriggers, W., Birmanns, S.: Using situs for flexible and rigid-body fitting of multiresolution single-molecule data. J. Struct. Biol. 133, 193–202 (2001)
Brigham, E.O.: The Fast Fourier Transform and its Applications. Prentice Hall, Upper Saddle River (1988)
Felzenszwalb, P.F., Huttenlocher, D.P.: Efficient graph-based image segmentation. Int. J.Comput. Vision 59, 167–181 (2004)
Cormen, T.H., Leiserson, C.E., Rivest, R.L.: Interoduction to Algorithms. The MIT Press, Cambridge (1990)
Dror, O., Benyamini, H., Nussinov, R., Wolfson, H.: MASS: multiple structural alignment by secondary structures. Bioinformatics 19 Suppl. 1, i95–i104 (2003)
Dror, O., Benyamini, H., Nussinov, R., Wolfson, H.: Multiple structural alignment by secondary structures:Algorithm and applications. Protein Sci. 12, 2492–2507 (2003)
Mehlhorn, K.: The LEDA Platform of Combinatorial and Geometric Computing. Cambridge University Press, United Kingdom (1999)
Kabsch, W.: A discussion of the solution for the best rotation to relate two sets of vectors. Acta Crystallogr A34, 827–828 (1978)
Murzin, A., Brenner, S., Hubbard, T., Chothia, C.: SCOP: a structural classification of proteins database for the investigation of sequences and structures. J. Mol. Biol. 247, 536–540 (1995)
Tagari, M., Newman, R., Chagoyen, M., Carazo, J., Henrick, K.: New electron microscopy database and deposition system. Trends. Biochem. Sci. 27, 589 (2002)
Inbar, Y., Benyamini, H., Nussinov, R., Wolfson, H.: Prediction of multimolecular assemblies by multiple docking. J. Mol. Biol. 349, 435–447 (2005)
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Lasker, K., Dror, O., Nussinov, R., Wolfson, H. (2005). Discovery of Protein Substructures in EM Maps. In: Casadio, R., Myers, G. (eds) Algorithms in Bioinformatics. WABI 2005. Lecture Notes in Computer Science(), vol 3692. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11557067_35
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DOI: https://doi.org/10.1007/11557067_35
Publisher Name: Springer, Berlin, Heidelberg
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