Rayner, LE;
Kadkhodayi-Kholghi, N;
Heenan, RK;
Gor, J;
Dalby, PA;
Perkins, SJ;
(2013)
The solution structure of rabbit IgG accounts for its interactions with the Fc receptor and complement C1q and its conformational stability.
Journal of Molecular Biology
, 425
(3)
506 - 523.
10.1016/j.jmb.2012.11.019.
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Abstract
Solution structures for antibodies are critical to understand function and therapeutic applications. The stability of the solution structure of rabbit IgG in different buffers and temperatures was determined by analytical ultracentrifugation and X-ray and neutron scattering. Rabbit IgG showed a principally monomeric species, which is well resolved from small amounts of a dimeric species. The proportion of dimer increased with increased concentration, decreased temperature and heavy water from 8% to 25% in all buffers except for high salt (250 mM NaCl). The Guinier X-ray radius of gyration R(G) likewise increased with concentration in 137 mM NaCl buffer but was unchanged in 250 mM NaCl buffer. The Guinier neutron R(G) values increased as the temperature decreased. The X-ray and neutron distance distribution curves P(r) revealed two peaks, M1 and M2, whose positions did not change with concentration to indicate unchanged structures under all these conditions. The maximum dimension increased with concentration because of dimer formation. Constrained scattering modeling reproducibly revealed very similar asymmetric solution structures for monomeric rabbit IgG in different buffers, in which the Fab-Fc and Fab-Fab pairs were separated by maximally extended hinge structures. The dimer was best modeled by two pairs of Fab regions forming tip-to-tip contacts. The intact rabbit IgG structures explained the ability of its two ligands, the Fc receptor and complement C1q, to bind to the top of its Fc region that is fully accessible and unhindered by the Fab regions.
| Type: | Article |
|---|---|
| Title: | The solution structure of rabbit IgG accounts for its interactions with the Fc receptor and complement C1q and its conformational stability. |
| Location: | UK |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jmb.2012.11.019 |
| Publisher version: | http://dx.doi.org/10.1016/j.jmb.2012.11.019 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Animals, Complement C1q, Immunoglobulin G, Neutron Diffraction, Protein Binding, Protein Conformation, Protein Multimerization, Rabbits, Receptors, Fc, Scattering, Small Angle, Ultracentrifugation, X-Ray Diffraction |
| UCL classification: | UCL 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: | https://discovery.ucl.ac.uk/id/eprint/1378726 |
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