X-ray and neutron scattering and analytical ultracentrifugation provide multiparameter structural and compositional information on proteins that complements high-resolution protein crystallography and NMR studies. They are ideal methods to use when either a large protein cannot be crystallized, when scattering provides the only means to obtain a solution structure, or the protein crystal structure has been determined and it is necessary to validate this. Once these results have been obtained, we apply automated constrained modelling methods based on known subunit crystal structures to identify the best-fit structure. Using our antibody structures as examples, we describe the generation of appropriate starting models, randomizing these for trial-and-error scattering fits, identifying the final best-fit models and interpreting these in terms of function. We discuss our structure determinations for IgA and IgD, an IgA–human serum albumin complex, the dimer of IgA and secretory component associated with this and chimaeras of mouse IgG with two complement proteins. Constrained modelling confirms the experimental data analysis and produces families of best-fit molecular models. Its usage has clarified several aspects of antibody structure and function in solution.
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February 2008
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Conference Article|
January 22 2008
Structure determinations of human and chimaeric antibodies by solution scattering and constrained molecular modelling
Stephen J. Perkins;
Stephen J. Perkins
1
1Department of Biochemistry and Molecular Biology, Darwin Building, University College London, Gower Street, London WC1E 6BT, U.K.
1To whom correspondence should be addressed (email s.perkins@medsch.ucl.ac.uk).
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Alexandra Bonner
Alexandra Bonner
1Department of Biochemistry and Molecular Biology, Darwin Building, University College London, Gower Street, London WC1E 6BT, U.K.
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Publisher: Portland Press Ltd
Received:
August 23 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (1): 37–42.
Article history
Received:
August 23 2007
Citation
Stephen J. Perkins, Alexandra Bonner; Structure determinations of human and chimaeric antibodies by solution scattering and constrained molecular modelling. Biochem Soc Trans 1 February 2008; 36 (1): 37–42. doi: https://doi.org/10.1042/BST0360037
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