The molecular dating game: an antibody heavy chain hangs loose with a chaperone while waiting for its life partner

Abstract

In a recent issue of Molecular Cell, Feige et al. (2009) utilize the murine immunoglobulin system to shed light on a long-standing puzzle: how do cells coordinate folding of different polypeptides that ultimately form a complex?

Figure 1. The Sequence of Events in Cellular Folding and Assembly of IgG Antibodies

(1) The unfolded C_H1 domain (red) of a newly synthesized IgG heavy chain is bound by BiP. (2) The intramolecular disulfide bond in the C_H1 domain (yellow) forms, possibly while the domain is bound to BiP, or upon its release, and most likely catalyzed by a PDI family member. (3) The C_H1 domain folds to its native structure (green) upon interaction with the complementary C_L domain within its partner light chain (gray structure). Peptidyl-proline isomerization must accompany native structure formation and most likely is catalyzed by an ER PPIase such as cyclophilin B. In this cartoon, we show only one of the two heavy and two light chains in the final assembled antibody.