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Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights

Perkins, SJ; Okemefuna, AI; Nan, R; Li, KY; Bonner, A; (2009) Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights. J R SOC INTERFACE , 6 S679 - S696. 10.1098/rsif.2009.0164.focus. Gold open access

Abstract

X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. They are useful when either a large protein cannot be crystallized, in which case scattering yields a solution structure, or a crystal structure has been determined and requires validation in solution. These solution structures are determined by the application of constrained modelling methods based on known subunit structures. First, an appropriate starting model is generated. Next, its conformation is randomized to generate thousands of models for trial-and-error fits. Comparison with the experimental data identifies a small family of best-fit models. Finally, their significance for biological function is assessed. We illustrate this in application to structure determinations for secretory immunoglobulin A, the most prevalent antibody in the human body and a first line of defence in mucosal immunity. We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. We discuss the importance of complementary data from analytical ultracentrifugation, and structural studies of protein-protein complexes. We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function.

Type: Article
Title: Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights
Open access status: An open access publication
DOI: 10.1098/rsif.2009.0164.focus
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC28439...
Keywords: immunoglobulin A, complement factor H, analytical ultracentrifugation, constrained modelling, neutron scattering, X-ray scattering, X-RAY-SCATTERING, EXTENDED SOLUTION STRUCTURE, BACK SOLUTION STRUCTURE, FACTOR-H, NEUTRON-SCATTERING, ANALYTICAL ULTRACENTRIFUGATION, HYDRODYNAMIC PROPERTIES, MACULAR DEGENERATION, SECRETORY COMPONENT, MUCOSAL IMMUNITY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: http://discovery.ucl.ac.uk/id/eprint/120953
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