title: 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.
authors.affiliation: Munich Center for Integrated Protein Science at the Department Chemie, Technische Universität München, 85748 Garching, Germany.
authors.forename: Roger
authors.initials: R
authors.lastname: Müller
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Gräwert
authors.forename: Thomas
authors.initials: T
authors.lastname: Kern
authors.forename: Tobias
authors.initials: T
authors.lastname: Madl
authors.forename: Jirka
authors.initials: J
authors.lastname: Peschek
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry*; D007075:Immunoglobulin M / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D058105:Polymerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D007141:Immunoglobulin Fc Fragments; D007075:Immunoglobulin M; D011994:Recombinant Proteins
keywords: antibody oligomerization; dimer interfaces; hybrid approach