Global structures of IgG isotypes expressing identical variable regions

Ertan Eryilmaz, Alena Janda, Jungwook Kim, Radames J B Cordero, David Cowburn, Arturo Casadevall

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Until relatively recently the immunoglobulin molecule was viewed as composed of two independent domains comprised of the variable (V) and constant (C) regions. However, recent work has established that the C region mediates allosteric changes in the V region that can influence specificity and affinity. To further explore cross-domain interrelationship in murine IgG structure we carried out solution small angle X-ray scattering (SAXS) measurements for four V region identical IgG isotypes. SAXS analysis revealed elongated Y-shaped structures in solution with significantly different, isotype-dependent domain orientations. To further explore local C region effects on the V region, the IgG3 Fab crystal structure from the same family was determined to 2.45Å resolution. The IgG3 Fab crystal structure differs from a closely related previously solved IgG1 Fab revealing significant structural differences, which may account for isotype-related specificity differences in V region identical Abs. Among the four murine isotypes, IgG3 was the most different in solution with regards to overall structure as well as aggregate formation in solution suggesting that the greater apparent affinity of this isotype resulted from polyvalent complexes with enhanced avidity. Our results provide additional evidence that Ig V and C domains influence each other structurally and suggest that V region structure can have significant effects on overall Ig structure.

Original languageEnglish (US)
Pages (from-to)588-598
Number of pages11
JournalMolecular Immunology
Volume56
Issue number4
DOIs
StatePublished - Dec 31 2013

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Immunoglobulin G
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Immunoglobulins

Keywords

  • Antigen
  • Constant domain
  • Immunoglobulin
  • Isotype
  • SAXS
  • Variable domain
  • X-ray crystallography

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology
  • Medicine(all)

Cite this

Global structures of IgG isotypes expressing identical variable regions. / Eryilmaz, Ertan; Janda, Alena; Kim, Jungwook; Cordero, Radames J B; Cowburn, David; Casadevall, Arturo.

In: Molecular Immunology, Vol. 56, No. 4, 31.12.2013, p. 588-598.

Research output: Contribution to journalArticle

Eryilmaz, E, Janda, A, Kim, J, Cordero, RJB, Cowburn, D & Casadevall, A 2013, 'Global structures of IgG isotypes expressing identical variable regions', Molecular Immunology, vol. 56, no. 4, pp. 588-598. https://doi.org/10.1016/j.molimm.2013.06.006
Eryilmaz, Ertan ; Janda, Alena ; Kim, Jungwook ; Cordero, Radames J B ; Cowburn, David ; Casadevall, Arturo. / Global structures of IgG isotypes expressing identical variable regions. In: Molecular Immunology. 2013 ; Vol. 56, No. 4. pp. 588-598.
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