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High-resolution structures of the IgM Fc domains reveal principles of its hexamer formation.

ABSTRACT: IgM is the first antibody produced during the humoral immune response. Despite its fundamental role in the immune system, IgM is structurally only poorly described. In this work we used X-ray crystallography and NMR spectroscopy to determine the atomic structures of the constant IgM Fc domains (Cµ2, Cµ3, and Cµ4) and to address their roles in IgM oligomerization. Although the isolated domains share the typical Ig fold, they differ substantially in dimerization properties and quaternary contacts. Unexpectedly, the Cµ4 domain and its C-terminal tail piece are responsible and sufficient for the specific polymerization of Cµ4 dimers into covalently linked hexamers of dimers. Based on small angle X-ray scattering data, we present a model of the ring-shaped Cµ4 structure, which reveals the principles of IgM oligomerization.

SUBMITTER: Muller R

PROVIDER: S-EPMC3690842 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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High-resolution structures of the IgM Fc domains reveal principles of its hexamer formation.

Müller Roger R Gräwert Melissa A MA Kern Thomas T Madl Tobias T Peschek Jirka J Sattler Michael M Groll Michael M Buchner Johannes J

Proceedings of the National Academy of Sciences of the United States of America 20130603 25

IgM is the first antibody produced during the humoral immune response. Despite its fundamental role in the immune system, IgM is structurally only poorly described. In this work we used X-ray crystallography and NMR spectroscopy to determine the atomic structures of the constant IgM Fc domains (Cµ2, Cµ3, and Cµ4) and to address their roles in IgM oligomerization. Although the isolated domains share the typical Ig fold, they differ substantially in dimerization properties and quaternary contacts. ...[more]

PMID: 23733956

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