How J-chain ensures the assembly of immunoglobulin IgM pentamers.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chiara Giannone, Xenia Mess, Ruiming He, Maria Rita Chelazzi, Annika Mayer, Anush Bakunts, Tuan Nguyen, Yevheniia Bushman, Andrea Orsi, Benedikt Gansen, Massimo Degano, Johannes Buchner, Roberto Sitia
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引用次数: 0

Abstract

Polymeric IgM immunoglobulins have high avidity for antigen and complement, and dominate primary antibody responses. They are produced either as assemblies of six µ2L2 subunits (i.e., hexamers), or as pentamers of two µ2L2 subunits and an additional protein termed J-chain (JC), which allows transcytosis across epithelia. The molecular mechanism of IgM assembly with the desired stoichiometry remained unknown. Here, we show in vitro and in cellula that JC outcompetes the sixth IgM subunit during assembly. Before insertion into IgM, JC exists as an ensemble of largely unstructured, protease-sensitive species with heterogeneous, non-native disulfide bonds. The J-chain interacts with the hydrophobic β-sheets selectively exposed by nascent pentamers. Completion of an amyloid-like core triggers JC folding and drives disulfide rearrangements that covalently stabilize JC-containing pentamers. In cells, the quality control factor ERp44 surveys IgM assembly and prevents the secretion of aberrant conformers. This mechanism allows the efficient production of high-avidity IgM for systemic or mucosal immunity.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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