The fab and fc fragments of IgA1 exhibit a different arrangement from that in IgG: a study by X-ray and neutron solution scattering and homology modelling 1 1Edited by R. Huber

Boehm, Mark K.; Woof, Jenny M.; Kerr, Michael A.; Perkins, Stephen J.

doi:10.1006/jmbi.1998.2556

Cited by 208 publications

(268 citation statements)

References 80 publications

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“…Molecular modeling predicts that Cys 133 will fold into the proximity of the terminal cysteine of the L chain. These same studies showed that HL disulfide bond formation could be restored to IgA2m (1) No crystal structure exists for IgA; however, molecular models of IgA1 have been published (15,16). In these models, displacement of the C H 2 domains was required to accommodate the glycosylation and disulfide-bonding pattern leading to steric crowding around the N-terminal region of the hinge compared with IgG1.…”

Section: Discussionmentioning

confidence: 99%

Cysteine Residues Required for the Attachment of the Light Chain in Human IgA2

Chintalacharuvu

Bhola

et al. 2002

The Journal of Immunology

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In humans, there are two subclasses of IgA, IgA1 and IgA2, with IgA2 existing as three allotypes, IgA2m(1), IgA2m(2) and IgA2(n). In IgA1, Cys133 in CH1 forms the disulfide bond to the L chain. Our previous studies indicated that in IgA2 lacking Cys133, a disulfide bond forms between the α-chain and the L chain when Cys220 is followed by Arg221, but not when Cys220 is followed by Pro221, suggesting that the Cys in CH1 might be involved in disulfide bonding to the L chain. However, here we show that covalent assembly of the H and L chains in IgA2(n) requires hinge-proximal Cys241 and Cys242 in CH2 and not Cys196 or Cys220 in CH1. Using pulse-chase experiments, we have demonstrated that wild-type IgA2(n) with Arg221 and Cys241 and Cys242 assembles through a disulfide-bonded HL intermediate. In contrast, the major intermediate for IgA2 m(1) with Pro221 assembly was H2 even though both Cys241 and Cys242 were present. Only a small fraction of IgA2 m(1) assembles through disulfide-bonded HL. Overall, our studies indicate that for IgA2 covalent assembly of the H and L chains requires the hinge-proximal cysteines in CH2 and that the structure of CH1 influences the efficiency with which this covalent bond forms.

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Section: Discussionmentioning

confidence: 99%

Cysteine Residues Required for the Attachment of the Light Chain in Human IgA2

Chintalacharuvu

Bhola

et al. 2002

The Journal of Immunology

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“…Because hydration shells are visible by x-rays, a hydration shell corresponding to 0.3 g of water/g of protein was created using HYPRO (31), giving an optimal total of 1607 spheres. The x-ray scattering curve I(Q) was calculated using the Debye equation adapted to spheres (16,32). Steric overlap between the Fab and Fc regions was assessed using the number of spheres n in each model, where models showing less than 95% of the required total of 1607 spheres (x-ray) or 1220 spheres (neutrons) were discarded.…”

Section: Methodsmentioning

confidence: 99%

The Solution Structures of Two Human IgG1 Antibodies Show Conformational Stability and Accommodate Their C1q and FcγR Ligands

Rayner

Hui

Gor

et al. 2015

Journal of Biological Chemistry

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Background:The human IgG1 antibody subclass is the most abundant one and is widely used in therapeutic applications. Results: Ultracentrifugation and x-ray/neutron scattering, together with atomistic modeling, revealed asymmetric concentration-independent IgG1 solution structures. Conclusion:The complement and receptor Fc binding sites are not hindered by the Fab regions, explaining its full activity. Significance: These solution structures clarify IgG1 activity and its therapeutic applications.

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“…6,7,9,45,46 The model of intact IgA1 was generated from published crystal and solution structures of IgA1. 47,48 N-and Oglycans were modeled using the GlyProt server and related databases (http://www. glycosciences.de), based on observed IgA1 glycoforms.…”

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confidence: 99%