Freezing immunoglobulins to see them move

L. Bongini, D. Fanelli, F. Piazza, P. De Los Rios, S. Sandin, U. Skoglund

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in different fields of molecular biology. In cryo-electron tomography experiments one may take several snapshots of a given biological macromolecule. In principle, a large enough collection of snapshots of the molecule may then be used to calculate its equilibrium configuration in terms of the experimentally accessible degrees of freedom and, hence, to estimate its potential energy. This information would be crucial in order to analyze the biological functions of biomolecules by directly accessing the relevant dynamical indicators. In this article, we analyze the results of cryo-electron tomography experiments performed on monoclonal murine IgG2a antibodies. We measure the equilibrium distribution of the molecule in terms of the relevant angular coordinates and build a mechanical model of the antibody dynamics. This approach enables us to derive an explicit expression of the IgG potential energy. Furthermore, we discuss the configuration space at equilibrium in relation to results from other techniques, and we set our discussion in the context of the current debate regarding conformation and flexibility of antibodies.
    Original languageEnglish
    Pages (from-to)6466-6471
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume101
    Issue number17
    DOIs
    Publication statusPublished - 27 Apr 2004

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