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

Roger Müller, Melissa A. Gräwert, Thomas Kern, Tobias Madl, Jirka Peschek, Michael Sattler, Michael Groll, Johannes Buchner

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish
Pages (from-to)10183-10188
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number25
DOIs
StatePublished - 18 Jun 2013

Keywords

  • Antibody oligomerization
  • Dimer interfaces
  • Hybrid approach

Fingerprint

Dive into the research topics of 'High-resolution structures of the IgM Fc domains reveal principles of its hexamer formation'. Together they form a unique fingerprint.

Cite this