Mega-Dalton biomolecular motion captured from electron microscopy reconstructions.

The vibrational analysis of elastic models suggests that the essential motions of large biomolecular assemblies can be captured efficiently at an intermediate scale without requiring knowledge of the atomic structure. While prior work has established a theoretical foundation for this analysis, we demonstrate here on experimental electron microscopy maps that vibrational modes indeed describe functionally relevant movements of macromolecular machines. The clamp closure in bacterial RNA polymerase, the ratcheting of 30S and 50S subunits of the ribosome, and the dynamic flexibility of chaperonin CCT are extracted directly from single electron microscopy structures at 15-27 A resolution. The striking agreement of the presented results with experimentally observed motions suggests that the motion of the large scale machinery in the cell is surprisingly independent of detailed atomic interactions and can be quite reasonably described as a motion of elastic bodies.

[1]  A. Lesk,et al.  Structural mechanisms for domain movements in proteins. , 1994, Biochemistry.

[2]  A. Cooper.  Dynamics of Proteins and Nucleic Acids , 1988 .

[3]  Willy Wriggers,et al.  Conformational flexibility of bacterial RNA polymerase , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Ming,et al.  How to describe protein motion without amino acid sequence and atomic coordinates , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[6]  K C Holmes,et al.  Normal modes as refinement parameters for the F-actin model. , 1995, Biophysical journal.

[7]  J. Frank,et al.  Solution Structure of the E. coli 70S Ribosome at 11.5 Å Resolution , 2000, Cell.

[8]  J. Mccammon,et al.  Situs: A package for docking crystal structures into low-resolution maps from electron microscopy. , 1999, Journal of structural biology.

[9]  P. Cramer,et al.  Structural Basis of Transcription : RNA Polymerase II at 2 . 8 Å Resolution , 2022 .

[10]  E A Merritt,et al.  Raster3D: photorealistic molecular graphics. , 1997, Methods in enzymology.

[11]  D. ben-Avraham,et al.  Normal mode analysis of G-actin. , 1993, Journal of molecular biology.

[12]  P. Freemont,et al.  Machinery of protein folding and unfolding. , 2002, Current opinion in structural biology.

[13]  K. Schulten,et al.  Principal Component Analysis and Long Time Protein Dynamics , 1996 .

[14]  C. Hunter,et al.  Sequence-dependent DNA structure: the role of the sugar-phosphate backbone. , 1998, Journal of molecular biology.

[15]  Fred L. Bookstein,et al.  Morphometric Tools for Landmark Data. , 1998 .

[16]  P. Cramer,et al.  Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution , 2001, Science.

[17]  N Go,et al.  Projection of monte carlo and molecular dynamics trajectories onto the normal mode axes: Human lysozyme , 1991, Proteins.

[18]  W. Wriggers,et al.  Exploring global distortions of biological macromolecules and assemblies from low-resolution structural information and elastic network theory. , 2002, Journal of molecular biology.

[19]  Bernd Fritzke,et al.  Growing cell structures--A self-organizing network for unsupervised and supervised learning , 1994, Neural Networks.

[20]  B M Pettitt,et al.  A sampling problem in molecular dynamics simulations of macromolecules. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  K. Severinov,et al.  Crystal Structure of Thermus aquaticus Core RNA Polymerase at 3.3 Å Resolution , 1999, Cell.

[22]  Jianpeng Ma,et al.  Domain movements in human fatty acid synthase by quantized elastic deformational model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Tosiyuki Noguti,et al.  Collective variable description of small-amplitude conformational fluctuations in a globular protein , 1982, Nature.

[24]  Tirion,et al.  Large Amplitude Elastic Motions in Proteins from a Single-Parameter, Atomic Analysis. , 1996, Physical review letters.

[25]  A. Leach.  Molecular Modelling: Principles and Applications , 1996 .

[26]  David A. Case,et al.  Normal mode analysis of biomolecular dynamics , 1997 .

[27]  Robert L. Jernigan,et al.  Dynamics of large proteins through hierarchical levels of coarse‐grained structures , 2002, J. Comput. Chem..

[28]  J. Frank,et al.  A model of protein synthesis based on cryo-electron microscopy of the E. coli ribosome , 1995, Nature.

[29]  J Martín-Benito,et al.  Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi‐native conformations , 2000, The EMBO journal.

[30]  A. Atilgan,et al.  Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential. , 1997, Folding & design.

[31]  Y. Sanejouand,et al.  Conformational change of proteins arising from normal mode calculations. , 2001, Protein engineering.

[32]  S Birmanns,et al.  Using situs for flexible and rigid-body fitting of multiresolution single-molecule data. , 2001, Journal of structural biology.

[33]  W Wriggers,et al.  Modeling tricks and fitting techniques for multiresolution structures. , 2001, Structure.

[34]  B. Alberts.  The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists , 1998, Cell.

[35]  Y. Sanejouand,et al.  Building‐block approach for determining low‐frequency normal modes of macromolecules , 2000, Proteins.

[36]  Joachim Frank,et al.  A ratchet-like inter-subunit reorganization of the ribosome during translocation , 2000, Nature.

[37]  Jeremy C. Smith,et al.  Correlated intramolecular motions and diffuse x–ray scattering in lysozyme , 1994, Nature Structural Biology.

[38]  J. Frank,et al.  A model of the translational apparatus based on a three-dimensional reconstruction of the Escherichia coli ribosome. , 1995, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[39]  K. Schulten,et al.  Self-organizing neural networks bridge the biomolecular resolution gap. , 1998, Journal of molecular biology.

[40]  M Tasumi,et al.  Normal vibrations of proteins: glucagon. , 1982, Biopolymers.