The crystal structure of the Fab fragment of the monoclonal antibody MAK33: Implications for folding and interaction with the chaperone BiP

The Fab fragment of the murine monoclonal antibody, MAK33, directed against human creatine kinase of the muscle-type, was crystallized and the three-dimensional structure was determined to 2.9Å. The antigen-binding surface of MAK33 shows a convex overall shape typical for immunoglobulins binding large antigens. The structure allows us to analyze the environment of cis-prolylpeptide bonds whose isomerization is of key importance in the folding process. These residues seem to be involved with not only domain stability but also seem to play a role in the association of heavy and light chains, reinforcing the importance of β-strand recognition in antibody assembly. The structure also allows the localization of segments of primary sequence postulated to represent binding sites for the ER-specific chaperone BiP within the context of the entire Fab fragment. These sequences are found primarily in β-strands that are necessary for interactions between the individual domains.