Identification of two rate-limiting steps in the degradation of partially folded immunoglobulin light chains

• DOI: 10.3389/fcell.2022.924848
• Publication Date: 2022-08-22T07:02:11Z
• Authors: Melissa J. Mann; Ashley R. Flory; Christina Oikonomou; Candace A. Hayes; Chris Melendez-Suchi; Linda M. Hendershot
• Keywords: Immunoglobulin domain; Folding (DSP implementation)

Antibody monomers are produced from two immunoglobulin heavy chains and light that folded assembled in the endoplasmic reticulum This process is assisted monitored by components of quality control machinery; an outcome made more fraught unusual genetic machinations employed to produce a seemingly unlimited antibody repertoire. Proper functioning adaptive immune system as dependent on success this operation, it ability identify degrade those molecules fail reach their native state. In study, rate-limiting steps were identified degradation non-secreted κ chain. Both focus constant domain (CL), which has evolved fold rapidly very stably serve catalyst for folding chain CH1 domain. The first hurdle reduction disulfide bond CL domain, required retrotranslocation cytosol. spite being reduced, retains structure, giving rise second step, unfolding at proteasome, results stalled intermediate.