Domain interactions stabilize the alternatively folded state of an antibody Fab fragment

Abstract
The structure of the Fab fragment of the monoclonal antibody MAK 33 (κ/IgG1) at pH 2 was characterized. Spectroscopic and kinetic analysis revealed a molten globule‐like state, characterized by elements of secondary structure but less defined tertiary contacts than in the native state. However, some aromatic side chains are in an asymmetrical environment. This structure was not detected using the isolated light chain or a Fab fragment lacking the covalent linkage of the light chain and Fd via the C‐terminal disulfide bond. Therefore, interactions between the two chains, stabilized by the interchain disulfide within the Fab fragment, are essential for formation of the alternatively folded state.