Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity

Anna Marie Davies; Rebecca Beavil; Momchil Barbolov; Balraj Sandhar; Hannah Gould; Andrew Beavil; Brian Sutton; James McDonnell

doi:10.1016/j.molimm.2023.05.006

Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity

Anna Marie Davies, Rebecca Beavil, Momchil Barbolov, Balraj Sandhar, Hannah Gould, Andrew Beavil, Brian Sutton, James McDonnell^*

^*Corresponding author for this work

Randall Centre of Cell & Molecular Biophysics

Research output: Contribution to journal › Article › peer-review

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Abstract

Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes.

Original language	English
Pages (from-to)	28-37
Number of pages	10
Journal	Molecular Immunology
Volume	159
DOIs	https://doi.org/10.1016/j.molimm.2023.05.006
Publication status	Published - 1 Jun 2023

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title = "Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity",

abstract = "Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 {\AA}. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes. ",

author = "Davies, {Anna Marie} and Rebecca Beavil and Momchil Barbolov and Balraj Sandhar and Hannah Gould and Andrew Beavil and Brian Sutton and James McDonnell",

note = "Funding Information: This work was supported by a grant from the Medical Research Council (Grant Reference MR/V010557/1). For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. We thank Diamond Light Source for access to beamline I04–1 (proposal number MX25301) that contributed to the results presented here, and the beamline staff for their support. Funding Information: This work was supported by a grant from the Medical Research Council (Grant Reference MR/V010557/1 ). For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. We thank Diamond Light Source for access to beamline I04–1 (proposal number MX25301) that contributed to the results presented here, and the beamline staff for their support. Publisher Copyright: {\textcopyright} 2023 The Authors",

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doi = "10.1016/j.molimm.2023.05.006",

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AU - Davies, Anna Marie

AU - Beavil, Rebecca

AU - Barbolov, Momchil

AU - Sandhar, Balraj

AU - Gould, Hannah

AU - Beavil, Andrew

AU - Sutton, Brian

AU - McDonnell, James

N1 - Funding Information: This work was supported by a grant from the Medical Research Council (Grant Reference MR/V010557/1). For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. We thank Diamond Light Source for access to beamline I04–1 (proposal number MX25301) that contributed to the results presented here, and the beamline staff for their support. Funding Information: This work was supported by a grant from the Medical Research Council (Grant Reference MR/V010557/1 ). For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. We thank Diamond Light Source for access to beamline I04–1 (proposal number MX25301) that contributed to the results presented here, and the beamline staff for their support. Publisher Copyright: © 2023 The Authors

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N2 - Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes.

AB - Antibodies of the IgD isotype remain the least well characterized of the mammalian immunoglobulin isotypes. Here we report three-dimensional structures for the Fab region of IgD, based on four different crystal structures, at resolutions of 1.45-2.75 Å. These IgD Fab crystals provide the first high-resolution views of the unique Cδ1 domain. Structural comparisons identify regions of conformational diversity within the Cδ1 domain, as well as among the homologous domains of Cα1, Cγ1 and Cμ1. The IgD Fab structure also possesses a unique conformation of the upper hinge region, which may contribute to the overall disposition of the very long linker sequence between the Fab and Fc regions found in human IgD. Structural similarities observed between IgD and IgG, and differences with IgA and IgM, are consistent with predicted evolutionary relationships for the mammalian antibody isotypes.

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Crystal structures of the human IgD Fab reveal insights into CH1 domain diversity

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