Conformation of human IgG subclasses in solution: Small‐angle X‐ray scattering and hydrodynamic studies

Ferenc KILÁR, István SIMON, Susan LAKATOS, Ferenc VONDERVISZT, György A. MEDGYESI, Péter ZÁVODSZKY

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Abstract

The structure of six human myeloma proteins: IgG1(Bal), IgG2(Klu), IgG3(Bak), IgG3(Het), IgG4(Kov) and IgG4(Pol), was studied in solution using small‐angle X‐ray scattering and hydrodynamic methods. For IgG1(Bal) and IgG3(Het) the experimental data, including radius of gyration (R°g), radii of gyration of the cross‐section (Rq1, Rq2), intrinsic viscosity [η], sedimentation coefficient (S320,w) and molecular mass, were interpreted in terms of structural models based on the Fab and Fc conformations, observed in crystal, by varying the relative positions of the Fab and Fc parts, i.e. their relative angles and distances. The values R°g= (6.00 ± 0.05) nm, S°20,W= (6.81 ± 0.10) S and [η] = 0.0062 ± 0.0005 cm3/mg obtained for IgG1(Bal) are compatible with a planar model in which the angle between the Fab arms is about 120°. For IgG3(Het) the following data were obtained: R°g= (4.90 ± 0.05) nm, S°20,W= (6.32 ± 0.01) S and [η] = (0.0065 ± 0.0005) cm3/mg. The apparent contradiction between the higher molecular mass and lower R°g and S°20,W values for IgG3(Het) in comparison to IgG1(Bal) can be resolved by proposing a “non‐planar” (tetrahedral) molecular shape, in which the long hinge peptide is in a folded conformation and the two Fab and Fc parts are in a closely packed arrangement. In this model the angle between the two Fab arms is about 90°, in the average position. The X‐ray scattering and hydrodynamic behaviour of the IgG2 and IgG4 types of antibodies appeared to be similar to IgG1(Bal). The parameters of the two IgG3 proteins are similar while they are different to the others.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalEuropean Journal of Biochemistry
Volume147
Issue number1
DOIs
Publication statusPublished - Feb 1985

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ASJC Scopus subject areas

  • Biochemistry

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