Solution Conformation and Segmental Flexibility of Immunoglobulins

Cathou, Renata E.

doi:10.1007/978-1-4684-0805-8_2

Cited by 17 publications

(15 citation statements)

References 147 publications

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“…9) 9 Model describing requirements for bivalent binding of one IgG molecule to a DNA fragment. The IgG drawing was based on that of Cathou (31). The angle at the hinge was taken at 115°; it is flexible, but to a minimal angle >80° (31 (32) where X is any base; it then acts as an exonuclease as well and can finally digest DNA to mono-and dinucleotides (32).…”

Section: Discussionmentioning

confidence: 99%

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Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs.

et al. 1980

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Section: Discussionmentioning

confidence: 99%

“…The IgG drawing was based on that of Cathou (31). The angle at the hinge was taken at 115°; it is flexible, but to a minimal angle >80° (31 (32) where X is any base; it then acts as an exonuclease as well and can finally digest DNA to mono-and dinucleotides (32). With limited digestion, it is possible to obtain mainly helical fragments.…”

Section: Discussionmentioning

confidence: 99%

Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs.

et al. 1980

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“…that the main structural site of this property is the hinge region (Noelken et al, 1965;Yguerabide et al, 1970;Cathou, 1978;Pecht, 1982). In a previous paper we have reported the assignment of the proton nuclear magnetic resonance (NMR) signals of the His-224,3 which exists in the hinge region of the IgGl immunoglobulins (Arata et al, 1980) (see Figure 1).…”

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confidence: 98%

Proton nuclear magnetic resonance study of human immunoglobulins G1 and their proteolytic fragments: structure of the hinge region and effects of a hinge region deletion on internal flexibility

Endo¹,

Arata²

1985

Biochemistry

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A high-resolution nuclear magnetic resonance (NMR) study is reported of human IgG immunoglobulins. Two kinds of myeloma proteins, IgGl Ike-N and IgGl Dob, were used in this study. IgGl Ike-N has an intact hinge, whereas the 15-residue segment Glu-216-Pro-230, which includes the disulfide-linked central region of the hinge Cys-226-Pro-227-Pro-228-Cys-229, is missing in IgGl Dob [Steiner, L. A., & Lopes, A. D. (1979) Biochemistry 18, 4054-4067]. It was observed that, upon saturation of the backbone CH proton resonances, spin diffusion is prevalent, resulting in a marked decrease in intensity of NMR signals that arise from rigid portions of the IgG molecules. NMR spectra thus obtained were compared for IgGl Ike-N and IgGl Dob. On the basis of the NMR measurements, it was possible to identify a number of resonances that originate from the hinge region of IgGl Ike-N. This indicates that spin diffusion extends much more slowly to the hinge region. The rate of saturation transfer through spin diffusion was compared for the two kinds of IgG proteins. It was shown that IgGl Dob, which still retains a part of the hinge segment from Ala-231 on, loses a significant degree of internal flexibility as compared to IgGl Ike-N. On the basis of the NMR measurements for the intact IgGl Ike-N and IgGl Dob as well as those of the Fab, F(ab')2. Fab', and Fc fragments of IgGl Ike-N, it is concluded that (1) segments and Pro-230-Leu-234, which precede and follow the disulfide-linked Cys-Pro-Pro-Cys part, respectively, are highly flexible, (2) the Pro-230-Leu-234 segment has an extended conformation and is less flexible than the Lys-222-Thr-225 segment, (3) having the Lys-222-Thr-225 segment is essential for the IgGl molecules to express a significant degree of flexibility, and (4) the two segments become comparable in flexibility when inter heavy chain disulfide bridges in the Cys-Pro-Pro-Cys part are reduced and alkylated. Without irradiation for the presaturation of the backbone CH proton resonances, it was possible to observe His resonances for the Fc region of the intact IgGl molecules. On the basis of the pH titration data for His-435, which exists in the interdomain CH2-CH3 contact, we have shown that the way in which the CH2 and CH3 domains contact with each other in the IgGl molecules changes very little (1) on cleavage of the Fab part, (2) on reduction and alkylation of the interchain disulfide bridges, and (3) on deletion of most of the hinge segment.Immunoglobulins that mediate antibody function consist of two distinct regions, i.e., Fab and Fc.1 The Fab region carries a recognition site for antigenic determinants, whereas the Fc region reacts with receptors of a variety of effector systems. Proteins of the human immunoglobulin G (IgG) class can be differentiated into four subclasses (IgGl through IgG4), each with a distinctive heavy chain, y\,y2, y3, or yA\ light chains can be of either X or k type, regardless of its heavy-chain subclass.2 The y chains consist of four homology units, VH, CH1, Ch2, and CH3, whereas the light...

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“…Another competing theory proposed an "all or none" switching mechanism, i.e. an allosteric model based on the assumption that immunoglobulins are, in fact, allosteric [6].…”

Section: Looking For Evidence Of Postulated Intra-molecular Immunologmentioning

confidence: 99%

Supramolecular Congo Red as Specific Ligand of Antibodies Engaged in Immune Complex

Jagusiak

Rybarska

Piekarska

et al. 2017

Self-Assembled Molecules – New Kind of Protein Ligands

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Supramolecular Congo red has been used to validate long-lasting theories regarding intramolecular signaling in antibodies and its relation to activation of the complement system. Strong enhancement of antigen-antibody complexation resulting from the binding of supramolecular ligands enables also polyclonal antibodies having intermediate affinity to trigger complement cascade apart of high affinity antibody fraction. This would not have been possible in the absence of Congo red. The property of antibodies provides specifically their ability to trigger the complement system allowed when sufficient structural strain is produced by antigen complexation provides an evidence of intramolecular signaling.The selective complexation of supramolecular ligands with antibodies engaged in immune complexes enables their using as carriers of drugs in immunotargeting system. Self-associating organic molecules which form ribbonlike micellar structures may, owing to their structural characteristics, penetrate inside proteins and form stable complexes. Such penetration is possible in areas of the protein which have been destabilized, either temporarily or permanently -such as antibody/antigen complexes. Since Congo red (CR) has been used in research as the most typical Keywords

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Solution Conformation and Segmental Flexibility of Immunoglobulins

Cited by 17 publications

References 147 publications

Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs.

Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs.

Proton nuclear magnetic resonance study of human immunoglobulins G1 and their proteolytic fragments: structure of the hinge region and effects of a hinge region deletion on internal flexibility

Supramolecular Congo Red as Specific Ligand of Antibodies Engaged in Immune Complex

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