Biophys. Struet. Mechanism 1, 139--146 (1975) 9 by Springer-Verlag t975 The Structure Determination of the Variable Portion of the Bence-Jones Protein Au H. Fehlhammer*, lg. Sehiffer**, O. Epp, P. M. Colman, E. E. Lattman***, P. Schwager, and W. Steigemarm Abteilung Strukturforschung I I and H. J. Schramm Abteilung Strukturforschung I, l~ax-Planck-Institut ffir ]~iochemie, Martinsried bei Miinchen und Physikaliseh Chemisches Institut der Technischen Universitiit Mfinchen Received September 23, t974 Abstract. The structure of a s-type Bence-Jones protein variable fragment Au has been determined by molecular replacement methods using the known structure of an other Bence- Jones variable fragment Rei (Epp et al., Eur. J. Biochem. 45, 5t3 (1974)). The crystallographic R factor is 0.3t for about 4000 significantly measured reflections between 6.8 to 2.5/%.. The Au protein forms a dimer across a crystallographic two fold axis. The spatial relationship of the two monomers, the conformation of the backbones and of the internal residnes is extremely similar to that found in Rei. Key words: Immunoglobulin -- Bence-Jones -- X-Ray -- Structure -- Rotation-Func- tion -- Patterson Search -- Translation Function -- Molecular Replacement. The structure of Fab fragments (Padlan et al., 1974; Pol]ak et al., 1973), a Benee-Jones dimer (Schiffer et al., i973) and a dimer made up of Bence-Jones protein (Rei) variable fragments (Epp et al., 1974), have been determined by X-ray diffraction. All three light chain domains show a very close structural resemblance. These domains are related by pseudo-two fold axes in the crystal, the structure of the dimer so formed seems to be identical in all three compounds. Assuming this similarity also holds for other light chain variable domains molecular replacement methods (for a review see Rossmann, 1972) may be applied. We have thus deter- mined the structure of the variable portion of the Bence-Jones protein Au, using the known structure of the l%ei protein. Proteins Au and Rei both belong to the ~1 subgroup and differ in only 16 amino acids, two of which are interchanges of glutamine for glutamic acid; see Table l (Palm and Hilsehmann, 1973; Sehiechl and Hilschmann, i971). The preparation, characterization and crystallization of the variable fragment of the Bence-Jones protein Au has been described (Schramm et al., 1970; Schramm, * Extract from Dissertation, Mfinehen (i974). ** on leave from the Division of Biological and lViedical Research, Argonne National Laboratory, Argonne, Illinois 60439, USA. *** Present Address: Rosenstiel Institute, Brandeis University, Waltham, Massachusetts 02154, USA.