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

The Feb fragment of the murine monoclonal antibody, MAK33, directed against human creatine kinase of the muscle-type, was crystallized and the three-d imensional structure was determined to 2.9 Angstrom. The antigen-binding su rface of MAK33 shows a convex overall shape typical for immunoglobulins bin ding large antigens, The structure allows us to analyze the environment of cis-prolylpeptide bonds whose isomerization is of key importance in the fol ding process. These residues seem to be involved with not only domain stabi lity but also seem to play a role in the association of heavy and light cha ins, reinforcing the importance of beta -strand recognition in antibody ass embly. The structure also allows the localization of segments of primary se quence postulated to represent binding sites for the ER-specific chaperone BiP within the context of the entire Feb fragment. These sequences are foun d primarily in beta -strands that are necessary for interactions between th e individual domains.