X-Ray Crystallographic Studies on the Combining Sites of Myeloma Proteins

X-Ray Crystallographic Studies on the Combining Sites of Myeloma Proteins 

The VL dimer Meg and the Fab fragments McPC 603 and Newm show the domain structure (Fig. 10). Each chain is built of two distinct compact globular subunits which form a distorted tetrahedron. The binding site is at the tip of the two VL and of VH and VL domains which are arranged at an angle to one another and oriented to form a cleft, groove, or cavity at the surface accessible to solvent. The angles between the CL and Ch domains and the VL and VH domains are not 

2 REI has recently been reported to bind one molecule of DNP (Huber, cited by Gavish et al., 1977). 

Residues 81-85 of the heavy chain, which Capra and Kehoe (1974) considered hypervariable in human heavy chains, are not part of the antibody combining site. They lie in a region exposed to solvent. Residues 84 and 85 are involved in a allotypic specificity in the rabbit (Mage, 1977), and the variation in the human VH chains may be associated with some function other than site complementarity. 

The problem of antibody complementarity thus resolves itself into the generation of different-shaped receptor sites upon a constant framework by substitution of sequences of one set of CDR of each chain by another. This has led to several attempts to construct models of antibody sites of a different specificity from the known structures. 

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