Small-angle neutron scattering and contrast variation: a powerful combination for studying biological structures.

The use of small-angle scattering (SAS) in the biological sciences continues to increase, driven as much by the need to study increasingly complex systems that are often resistant to crystallization or are too large for NMR as by the availability of user facilities and advancements in the modelling of biological structures from SAS data. SAS, whether with neutrons (SANS) or X-rays (SAXS), is a structural probe of length scales ranging from 10 to 10,000 Å. When applied to biological complexes in dilute solution, it provides size and shape information that can be used to produce structural models that can provide insight into function. SANS enables the use of contrast-variation methods through the unique interaction of neutrons with hydrogen and its isotope deuterium. SANS with contrast variation enables the visualization of components within multisubunit complexes, making it a powerful tool for probing protein-protein and protein-nucleic acid complexes, as well as the interaction of proteins with lipids and detergents.

[1]  J. Stull,et al.  Neutron-scattering studies reveal further details of the Ca2+/calmodulin-dependent activation mechanism of myosin light chain kinase. , 1998, Biochemistry.

[2]  Anne Marie Augustus,et al.  Structural Basis for the Differential Regulation of DNA by the Methionine Repressor MetJ* , 2006, Journal of Biological Chemistry.

[3]  M. B. Cardoso,et al.  Insight into the structure of light-harvesting complex II and its stabilization in detergent solution. , 2009, The journal of physical chemistry. B.

[4]  J. Trewhella,et al.  Troponin I encompasses an extended troponin C in the Ca(2+)-bound complex: a small-angle X-ray and neutron scattering study. , 1994, Biochemistry.

[5]  J. Trewhella,et al.  A model structure of the muscle protein complex 4Ca2+.troponin C.troponin I derived from small-angle scattering data: implications for regulation. , 1994, Biochemistry.

[6]  D. Engelman,et al.  Positions of proteins S14, S18 and S20 in the 30 S ribosomal subunit of Escherichia coli. , 1984, Journal of molecular biology.

[7]  Elina Tjioe,et al.  ORNL_SAS: software for calculation of small-angle scattering intensities of proteins and protein complexes , 2007 .

[8]  Jill Trewhella,et al.  The structure of the KinA-Sda complex suggests an allosteric mechanism of histidine kinase inhibition. , 2007, Journal of molecular biology.

[9]  Edward Eisenstein,et al.  Interaction of GroEL and GroEL/GroES complexes with a nonnative subtilisin variant: a small-angle neutron scattering study. , 2003, Journal of structural biology.

[10]  P. Timmins,et al.  The structure of rice dwarf virus determined by small-angle neutron scattering measurements. , 1985, Virology.

[11]  D. Svergun,et al.  Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. I. Invariants and validation of electron microscopy models. , 1997, Journal of molecular biology.

[12]  P. Timmins,et al.  A neutron scattering study of the structure of compact and swollen forms of southern bean mosaic virus. , 1982, Virology.

[13]  J. Stull,et al.  Structures of calmodulin and a functional myosin light chain kinase in the activated complex: a neutron scattering study. , 1997, Biochemistry.

[14]  A. M. Bueche,et al.  Scattering by an Inhomogeneous Solid , 1949 .

[15]  W. A. King,et al.  Solution structure of the chicken skeletal muscle troponin complex via small-angle neutron and X-ray scattering. , 2005, Journal of molecular biology.

[16]  Jill Trewhella,et al.  Synaptic arrangement of the neuroligin/beta-neurexin complex revealed by X-ray and neutron scattering. , 2007, Structure.

[17]  D. Doyle,et al.  Structural characterization and pH-induced conformational transition of full-length KcsA. , 2006, Biophysical journal.

[18]  P. Timmins,et al.  The effect of regulatory Ca2+ on the in situ structures of troponin C and troponin I: a neutron scattering study. , 1998, Journal of molecular biology.

[19]  I. Tsaneva,et al.  A synthetic holliday junction is sandwiched between two tetrameric Mycobacterium leprae RuvA structures in solution: new insights from neutron scattering contrast variation and modelling. , 1998, Journal of Molecular Biology.

[20]  K. Ibel Comparison of neutron and X-ray scattering of dilute myoglobin solutions. , 1975, Journal of molecular biology.

[21]  J. Trewhella,et al.  Quaternary Structures of a Catalytic Subunit-Regulatory Subunit Dimeric Complex and the Holoenzyme of the cAMP-dependent Protein Kinase by Neutron Contrast Variation* , 1998, The Journal of Biological Chemistry.

[22]  D I Svergun,et al.  A Map of Protein-rRNA Distribution in the 70 SEscherichia coli Ribosome* , 2000, The Journal of Biological Chemistry.

[23]  Jill Trewhella,et al.  MULCh: modules for the analysis of small-angle neutron contrast variation data from biomolecular assemblies , 2008 .

[24]  D. Svergun,et al.  Structural model of the 50 S subunit of Escherichia coli ribosomes from solution scattering. II. Neutron scattering study. , 1994, Journal of molecular biology.

[25]  P. Rosevear,et al.  The solution structure of a cardiac troponin C-troponin I-troponin T complex shows a somewhat compact troponin C interacting with an extended troponin I-troponin T component. , 2002, Biochemistry.

[26]  C. O’Connell,et al.  Bacteriophage MS2: molecular weight and spatial distribution of the protein and RNA components by small-angle neutron scattering and virus counting. , 2003, Structure.

[27]  Derek Ho,et al.  Structure-specific DNA-induced Conformational Changes in Taq Polymerase Revealed by Small Angle Neutron Scattering* , 2004, Journal of Biological Chemistry.

[28]  J. E. Mellema,et al.  Structure and composition of influenza virus. A small-angle neutron scattering study. , 1985, Journal of molecular biology.

[29]  John A. Tainer,et al.  X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution , 2007, Quarterly Reviews of Biophysics.

[30]  J. Wang,et al.  The solution structure of the DNA double-stranded break repair protein Ku and its complex with DNA: a neutron contrast variation study. , 1999, Biochemistry.

[31]  Susan S. Taylor,et al.  C Subunits Binding to the Protein Kinase A RIα Dimer Induce a Large Conformational Change* , 2004, Journal of Biological Chemistry.

[32]  B. Jacrot,et al.  Structure of the tomato bushy stunt virus: a model for protein-RNA interaction. , 1978, Journal of molecular biology.

[33]  B. Jacrot,et al.  Comparative neutron small-angle scattering study of small spherical RNA viruses , 1977, Nature.

[34]  P. Rosevear,et al.  Small-angle neutron scattering with contrast variation reveals spatial relationships between the three subunits in the ternary cardiac troponin complex and the effects of troponin I phosphorylation. , 2003, Biochemistry.

[35]  D. Svergun,et al.  Small-angle scattering studies of biological macromolecules in solution , 2003 .

[36]  Masao Kakudo,et al.  Small Angle Scattering of X-Rays , 1968 .

[37]  J. Trewhella,et al.  Calmodulin remains extended upon binding to smooth muscle caldesmon: a combined small-angle scattering and fourier transform infrared spectroscopy study. , 2000, Biochemistry.

[38]  E. Seymann,et al.  Neutron scattering lengths: A survey of experimental data and methods , 1991 .

[39]  Z. Bu,et al.  Ezrin induces long-range interdomain allostery in the scaffolding protein NHERF1. , 2009, Journal of molecular biology.

[40]  D. Engelman,et al.  Neutron-scattering studies of the ribosome of Escherichia coli: a provisional map of the locations of proteins S3, S4, S5, S7, S8 and S9 in the 30 S subunit. , 1978, Journal of molecular biology.

[41]  B. Jacrot,et al.  REVIEW ARTICLE: The study of biological structures by neutron scattering from solution , 1976 .

[42]  J A Langer,et al.  A complete mapping of the proteins in the small ribosomal subunit of Escherichia coli. , 1987, Science.

[43]  D. Svergun,et al.  Structural model of the 50 S subunit of Escherichia coli ribosomes from solution scattering. I. X-ray synchrotron radiation study. , 1994, Journal of molecular biology.

[44]  J. E. Mellema,et al.  An investigation of the structure of alfalfa mosaic virus by small-angle neutron scattering. , 1981, Journal of molecular biology.

[45]  D. Engelman,et al.  Positions of proteins S6, S11 and S15 in the 30 S ribosomal subunit of Escherichia coli. , 1981, Journal of molecular biology.

[46]  F. Kull,et al.  The shapes of the motor domains of two oppositely directed microtubule motors, ncd and kinesin: a neutron scattering study. , 1995, Biophysical journal.

[47]  D. Svergun,et al.  Solution scattering structural analysis of the 70 S Escherichia coli ribosome by contrast variation. II. A model of the ribosome and its RNA at 3.5 nm resolution. , 1997, Journal of molecular biology.

[48]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[49]  K. Kobayashi,et al.  Crystal structure of human serum albumin at 2.5 A resolution. , 1999, Protein engineering.