title: The crystal structure of the fab fragment of the monoclonal antibody MAK33. Implications for folding and interaction with the chaperone bip.
abstract: 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 2.9 A. 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-prolyl-peptide 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 beta-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 beta-strands that are necessary for interactions between the individual domains.
authors.affiliation: Dana-Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Augustine
authors.forename: A
authors.initials: A
authors.lastname: de La Calle
authors.forename: G
authors.initials: G
authors.lastname: Knarr
authors.forename: J
authors.initials: J
authors.lastname: Buchner
authors.forename: C A
authors.initials: CA
authors.lastname: Frederick
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003402:Creatine Kinase / Q000276:immunology; D018360:Crystallography, X-Ray; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007140:Immunoglobulin Fab Fragments; D018832:Molecular Chaperones; D010446:Peptide Fragments; D003402:Creatine Kinase