Understanding the biosynthesis of human IgM SAM-6 through a combinatorial expression of mutant subunits that affect product assembly and secretion.

ABSTRACT: Polymeric IgMs are secreted from plasma cells abundantly despite their structural complexity and intricate multimerization steps. To gain insights into IgM's assembly mechanics that underwrite such high-level secretion, we characterized the biosynthetic process of a natural human IgM, SAM-6, using a heterologous HEK293(6E) cell platform that allowed the production of IgMs both in hexameric and pentameric forms in a controlled fashion. By creating a series of mutant subunits that differentially disrupt secretion, folding, and specific inter-chain disulfide bond formation, we assessed their effects on various aspects of IgM biosynthesis in 57 different subunit chain combinations, both in hexameric and pentameric formats. The mutations caused a spectrum of changes in steady-state subcellular

SUBMITTER: Hasegawa H 

PROVIDER: S-EPMC11161108 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature