Abstract
AbstractPolymeric (p) immunoglobulins (Igs) serve broad functions during vertebrate immune responses. Typically, pIgs contain between two and six Ig monomers, each with two antigen binding fragments and one fragment crystallization (Fc). In addition, many pIgs assemble with a joining-chain (JC); however, the number of monomers and potential to include JC vary with species and heavy chain class. Here, we report the cryo-electron microscopy structure of IgM from a teleost (t) species, which does not encode JC. The structure reveals four tIgM Fcs linked through eight C-terminal tailpieces (Tps), which adopt a single β-sandwich-like domain (Tp assembly) located between two Fcs. Specifically, two of eight heavy chains fold uniquely, resulting in a structure distinct from mammalian IgM, which typically contains five IgM monomers, one JC and a centrally-located Tp assembly. Together with mutational analysis, structural data indicate that pIgs have evolved a range of assembly mechanisms and structures, each likely to support unique antibody effector functions.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference56 articles.
1. Flajnik, M. F. & Kasahara, M. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat. Rev. Genet 11, 47–59 (2010).
2. Chapuis, R. M. & Koshland, M. E. Linkage and assembly of polymeric IgA immunoglobulins. Biochemistry 14, 1320–1326 (1975).
3. Wiersma, E. J. & Shulman, M. J. Assembly of IgM. Role of disulfide bonding and noncovalent interactions. J. Immunol. 154, 5265–5272 (1995).
4. Hohman, V. S. et al. J Chain in the Nurse Shark: Implications for Function in a Lower Vertebrate. J. Immunol. 170, 6016–6023 (2003).
5. Hadjiazimi, I. & Micheahamzehpour, M. XENOPUS-LAEVIS 19S IMMUNOGLOBULIN - ULTRASTRUCTURE AND J-CHAIN ISOLATION. IMMUNOLOGY 30, 587–591 (1976).