The structure of the teleost Immunoglobulin M core provides insights on polymeric antibody evolution, assembly, and function.
| Autor: | Lyu M; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 USA., Malyutin AG; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 USA.; Beckman Institute, California Institute of Technology, Pasadena, CA 91125 USA.; Present address, Takeda Development Center Americas, San Diego, California 92121., Stadtmueller BM; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 USA.; Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 05. Date of Electronic Publication: 2023 Sep 05. |
| DOI: | 10.1101/2023.03.29.534771 |
| Abstrakt: | Polymeric (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 varies 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 revealed four tIgM Fcs linked through eight C-terminal tailpieces (Tps), which adopt a single β-sandwich-like domain (Tp assembly) located between two Fcs. Remarkably, 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. Competing Interests: COMPETING INTERESTS. BMS and ML are listed as inventors on a provisional patent application that includes the design, production and use of chimeric antibodies, some of which include teleost Ig heavy chain motifs. |
| Databáze: | MEDLINE |
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