Evidence for mobility of immunoglobulin domains obtained by spin-label method

Kaivarainen, Alex; Nezlin, Roald

doi:10.1016/0006-291x(76)90039-5

Cited by 16 publications

(5 citation statements)

References 6 publications

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“…1 B. On the other hand, Feinstein and Rowe (1965), and Valentine and Green (1967) performed electron microscopy studies, and they suggested that the angle between Fab segments of IgG molecules vary widely. Their suggestion is supported by many studies such as NMR (Arata et al, 1980), EPR spectroscopy (Käiväräinen and Nezlin, 1976), electron microscopy (Roux et al, 1997), and theoretical studies (McCammon and Karplus, 1977). Especially, Hanson et al (1981) performed a dynamical study using nanosecond fluorescence spectroscopy, and reported that wagging or cone-like wobbling motions of the Fab fragments are possible on the hinge region.…”

Section: Introductionmentioning

confidence: 82%

Molecular Dynamics of Hinge-Bending Motion of IgG Vanishing with Hydrolysis by Papain

Hayashi

Miura²,

Isobe

et al. 2000

Biophysical Journal

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We have performed dielectric relaxation measurements via a time domain reflectometry (TDR) method to study dynamic behaviors of the segmental flexibility of immunoglobulin G (IgG) in aqueous solution without antigen binding. In general, an intermediate relaxation process due to bound water is observed around 100 MHz at 25 degrees C for common proteins between two relaxation processes due to overall rotation and reorientation of free water. However, the intermediate process observed around 6 MHz for IgG was due to both bound water and hinge-bending motion. The apparent activation energy of 33 kJ/mol was larger than 27 kJ/mol for only bound water, and the relaxation strength was about five times as large as expected for bound water. The shape of the relaxation curve was very broad and asymmetric. These characteristic differences arising from the hinge-bending motion of IgG disappeared for fragments decomposed from IgG hydrolyzed by papain, since the hinge-bending motion did not exist in this case. We have separated the relaxation processes due to hinge-bending motion and bound water for IgG and obtained the Fab-Fab angle of IgG as about 130 degrees by Kirkwood's correlation parameter and the activation energy of 34 kJ/mol for hinge-bending motion.

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Section: Introductionmentioning

confidence: 82%

Molecular Dynamics of Hinge-Bending Motion of IgG Vanishing with Hydrolysis by Papain

Hayashi

Miura²,

Isobe

et al. 2000

Biophysical Journal

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“…The V module contains the antigen binding site, and the C module contains the hinge region that connects the arm to the Fc portion of the intact molecule; switch peptides (not shown) connect the two modules. X-ray diffraction (Huber et al, 1976;Edmundson et al, 1978), spin-label (Kaivarainen & Nezlin, 1976), and theoretical studies (McCammon & Karplus, 1977) suggest that the Fab domains exhibit restricted flexibility. The rather open switch region connecting the V and C globular modules is the proposed site of flexibility.…”

Section: Theoretical Calculations and Discussionmentioning

confidence: 99%

Segmental flexibility of immunoglobulin G antibody molecules in solution: a new interpretation

Hanson¹,

Yguerabide²,

Schumaker³

1981

Biochemistry

115

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We propose a new model for the segmental flexibility of immunoglobulin G (IgG). The flexibility of native and mildly reduced anti-5-(dimethylamino)naphthalene-1-sulfonyl (anti-dansyl) antibody was reexamined by nanosecond fluorescence spectroscopy using deconvolution and lamp-shift corrections. The rabbit antibodies used for this study were purified of dimers and other aggregates. The original results indicated that the decay of fluorescence anisotropy involved two rotational correlation times. It was suggested that the short rotational correlation time, phi s, represented a flexible Fab arm motion over a restricted angle and that the long correlation time, phi L, represented global tumbling of the molecule [Yguerabide, J., Epstein, H. F., & Stryer, L. (1970) J. Mol. Biol. 51, 573--590]. Our new data indicate that the long correlation time primarily represents motions of the Fab segments and not global tumbling of the entire molecule. This interpretation implies a more flexible model for IgG. Thus, in solution the antibody arms appear to move over a wide angle and are not restricted to 33 degrees as was suggested in the earlier model. Simple diffusion calculations and other evidence suggest that phi s may represent V-module flexibility about the switch peptides or Fab twisting around its long axis, whereas phi L may represent wagging or wobbling motions of the Fab arms about the hinge region. The faster motions appear to occur over small angles whereas the slower wagging or wobbling motions responsible for most of the decay of anisotropy appear to be much less restricted. The biological function of IgG and anisotropy changes resulting from hinge disulfide cleavage are interpreted in terms of the proposed model. We also demonstrate a useful method for comparison of time-dependent and steady-state fluorescence polarization data.

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“…While the latter shows the Fab arms in a T configuration, I have drawn them in a Y configuration in the diagram. There is evidence for some fiexibility in IgE (Kaivarainen & Nezlin 1976) and other immunoglobulins, so that the Y configuration with the combining sites about 9 nm apart may more accurately refiect the average position in solution (Werner et al 1972).…”

Section: A Igementioning

confidence: 99%

The IgE‐Mast Cell System as a Paradigm for the Study of Antibody Mechanisms

Metzger

1978

Immunological Reviews

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Evidence for mobility of immunoglobulin domains obtained by spin-label method

Cited by 16 publications

References 6 publications

Molecular Dynamics of Hinge-Bending Motion of IgG Vanishing with Hydrolysis by Papain

Molecular Dynamics of Hinge-Bending Motion of IgG Vanishing with Hydrolysis by Papain

Segmental flexibility of immunoglobulin G antibody molecules in solution: a new interpretation

The IgE‐Mast Cell System as a Paradigm for the Study of Antibody Mechanisms

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